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Salden S, Xu Y, De Smet S, Peremans K, Dobbeleir A, De Witte S, Van Eeckhaut A, Saunders JH, Haverbeke A, Baeken C. Investigating cerebral blood flow in anxious dogs: a 99mTc-HMPAO SPECT imaging study. Res Vet Sci 2025; 190:105648. [PMID: 40245449 DOI: 10.1016/j.rvsc.2025.105648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 01/17/2025] [Accepted: 04/06/2025] [Indexed: 04/19/2025]
Abstract
Anxiety-related disorders have a significant effect on the welfare of pet dogs, often leading to behavioral problems and straining the human-animal bond. Conventional treatments sometimes prove inadequate, highlighting the need for a more objective understanding of the neurobiological pathways underlying canine anxiety disorders. Therefore, this study aimed to investigate anxiety disorders in dogs using 99mTc-HMPAO single photon emission computed tomography (SPECT), focusing on the left frontal region, subcortical region, and cerebellum. While a frequentist approach found no significant differences in brain perfusion between patient and healthy dogs, Bayesian analyses indicated underpowered results. Subsequent correlational analyses were performed and revealed significant positive associations between cerebellar perfusion and aggression, social fear, and nonsocial fear C-BARQ cluster scores (Canine Behavioral Assessment and Research Questionnaire), as well as a negative correlation between subcortical perfusion and nonsocial fear C-BARQ cluster scores in dogs with an anxiety disorder. This study supports the involvement of subcortical regions in anxious dogs and emphasizes the emerging role of the cerebellum in canine anxiety disorders. This study deepens our understanding of the neural correlates of canine anxiety and underscores the potential of nuclear neuroimaging in clinical practice. Future research into broader neural functioning is warranted for improved diagnostic and therapeutic strategies in veterinary behavioral medicine.
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Affiliation(s)
- Sofie Salden
- Department of Morphology, Imaging, Orthopedics, Rehabilitation, and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium.
| | - Yangfeng Xu
- Department of Morphology, Imaging, Orthopedics, Rehabilitation, and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium
| | - Stefanie De Smet
- Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Brain Stimulation and Cognition (BSC) Lab, Department of Cognitive Neuroscience, Faculty of Psychology & Neuroscience, Maastricht University, Oxfordlaan 55, 6229 EV Maastricht, The Netherlands
| | - Kathelijne Peremans
- Department of Morphology, Imaging, Orthopedics, Rehabilitation, and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
| | - Andre Dobbeleir
- Department of Morphology, Imaging, Orthopedics, Rehabilitation, and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
| | - Sara De Witte
- Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Department of Neurology and Bru-BRAIN, University Hospital (UZ Brussel), Brussels, Belgium; Neuroprotection & Neuromodulation Research Group (NEUR), Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium
| | - Ann Van Eeckhaut
- Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium
| | - Jimmy H Saunders
- Department of Morphology, Imaging, Orthopedics, Rehabilitation, and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
| | - Anouck Haverbeke
- Department of Morphology, Imaging, Orthopedics, Rehabilitation, and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
| | - Chris Baeken
- Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Vrije Universiteit Brussel (VUB), Department of Psychiatry, University Hospital (UZBrussel), Brussels, Belgium; Department of Electrical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands.
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Isparta S, Töre-Yargın G, Wagner SC, Mundorf A, Cinar Kul B, Da Graça Pereira G, Güntürkün O, Ocklenburg S, Freund N, Salgirli Demirbas Y. Measuring paw preferences in dogs, cats and rats: Design requirements and innovations in methodology. Laterality 2024; 29:246-282. [PMID: 38669348 DOI: 10.1080/1357650x.2024.2341459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 04/04/2024] [Indexed: 04/28/2024]
Abstract
Studying behavioural lateralization in animals holds great potential for answering important questions in laterality research and clinical neuroscience. However, comparative research encounters challenges in reliability and validity, requiring new approaches and innovative designs to overcome. Although validated tests exist for some species, there is yet no standard test to compare lateralized manual behaviours between individuals, populations, and animal species. One of the main reasons is that different fine-motor abilities and postures must be considered for each species. Given that pawedness/handedness is a universal marker for behavioural lateralization across species, this article focuses on three commonly investigated species in laterality research: dogs, cats, and rats. We will present six apparatuses (two for dogs, three for cats, and one for rats) that enable an accurate assessment of paw preference. Design requirements and specifications such as zoometric fit for different body sizes and ages, reliability, robustness of the material, maintenance during and after testing, and animal welfare are extremely important when designing a new apparatus. Given that the study of behavioural lateralization yields crucial insights into animal welfare, laterality research, and clinical neuroscience, we aim to provide a solution to these challenges by presenting design requirements and innovations in methodology across species.
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Affiliation(s)
- Sevim Isparta
- Biopsychology, Institute of Cognitive Neuroscience, Department of Psychology, Ruhr University Bochum, Bochum, Germany
- Department of Genetics, Faculty of Veterinary Medicine, Ankara University, Ankara, Turkey
- Division of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr University Bochum, Bochum, Germany
| | - Gülşen Töre-Yargın
- Brunel Design School College of Engineering Design & Physical Sciences, Brunel University London, Uxbridge, UK
- METU/BILTIR-UTEST Product Usability Unit, Department of Industrial Design, Middle East Technical University, Ankara, Turkey
| | - Selina C Wagner
- Division of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr University Bochum, Bochum, Germany
| | - Annakarina Mundorf
- Institute for Systems Medicine and Department of Human Medicine, MSH Medical School Hamburg, Hamburg, Germany
- Department of Neurology, Division of Cognitive Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Bengi Cinar Kul
- Department of Genetics, Faculty of Veterinary Medicine, Ankara University, Ankara, Turkey
| | - Goncalo Da Graça Pereira
- Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Almada, Portugal
| | - Onur Güntürkün
- Biopsychology, Institute of Cognitive Neuroscience, Department of Psychology, Ruhr University Bochum, Bochum, Germany
- Research Center One Health Ruhr, Research Alliance Ruhr, Ruhr University Bochum, Bochum, Germany
| | - Sebastian Ocklenburg
- Biopsychology, Institute of Cognitive Neuroscience, Department of Psychology, Ruhr University Bochum, Bochum, Germany
- Department of Psychology, MSH Medical School Hamburg, Hamburg, Germany
- ICAN Institute for Cognitive and Affective Neuroscience, MSH Medical School Hamburg, Hamburg, Germany
| | - Nadja Freund
- Division of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr University Bochum, Bochum, Germany
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Amirhosseini MH, Yadav V, Serpell JA, Pettigrew P, Kain P. An artificial intelligence approach to predicting personality types in dogs. Sci Rep 2024; 14:2404. [PMID: 38286813 PMCID: PMC10825194 DOI: 10.1038/s41598-024-52920-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 01/25/2024] [Indexed: 01/31/2024] Open
Abstract
Canine personality and behavioural characteristics have a significant influence on relationships between domestic dogs and humans as well as determining the suitability of dogs for specific working roles. As a result, many researchers have attempted to develop reliable personality assessment tools for dogs. Most previous work has analysed dogs' behavioural patterns collected via questionnaires using traditional statistical analytic approaches. Artificial Intelligence has been widely and successfully used for predicting human personality types. However, similar approaches have not been applied to data on canine personality. In this research, machine learning techniques were applied to the classification of canine personality types using behavioural data derived from the C-BARQ project. As the dataset was not labelled, in the first step, an unsupervised learning approach was adopted and K-Means algorithm was used to perform clustering and labelling of the data. Five distinct categories of dogs emerged from the K-Means clustering analysis of behavioural data, corresponding to five different personality types. Feature importance analysis was then conducted to identify the relative importance of each behavioural variable's contribution to each cluster and descriptive labels were generated for each of the personality traits based on these associations. The five personality types identified in this paper were labelled: "Excitable/Hyperattached", "Anxious/Fearful", "Aloof/Predatory", "Reactive/Assertive", and "Calm/Agreeable". Four machine learning models including Support Vector Machine (SVM), K-Nearest Neighbour (KNN), Naïve Bayes, and Decision Tree were implemented to predict the personality traits of dogs based on the labelled data. The performance of the models was evaluated using fivefold cross validation method and the results demonstrated that the Decision Tree model provided the best performance with a substantial accuracy of 99%. The novel AI-based methodology in this research may be useful in the future to enhance the selection and training of dogs for specific working and non-working roles.
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Affiliation(s)
- Mohammad Hossein Amirhosseini
- Department of Computer Science and Digital Technologies, School of Architecture, Computing and Engineering, University of East London, London, UK.
| | - Vinaykumar Yadav
- Department of Computer Science and Digital Technologies, School of Architecture, Computing and Engineering, University of East London, London, UK
| | - James A Serpell
- School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Xu Y, Peremans K, Salden S, Audenaert K, Dobbeleir A, Van Eeckhaut A, De Bundel D, Saunders JH, Baeken C. Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs. Front Vet Sci 2023; 10:1154596. [PMID: 37261109 PMCID: PMC10228829 DOI: 10.3389/fvets.2023.1154596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 05/03/2023] [Indexed: 06/02/2023] Open
Abstract
Aim The neurobiological effects of repetitive transcranial magnetic stimulation are believed to run in part through the dopaminergic system. Accelerated high frequency rTMS (aHF-rTMS), a new form of stimuli delivery, is currently being tested for its usefulness in treating human and canine mental disorders. However, the short-and long-term neurobiological effects are still unclear, including the effects on the dopaminergic system. In aHF-rTMS, multiple sessions are delivered within 1 day instead of one session per day, not only to accelerate the time to response but also to increase clinical efficacy. To gain more insight into the neurobiology of aHF-rTMS, we investigated whether applying five sessions in 1 day has direct and/or delayed effects on the dopamine transporter (DAT), and on dopamine metabolites of cerebrospinal fluid (CSF) in beagles. Materials and methods Thirteen beagles were randomly divided into two groups: five active stimulation sessions (n = 9), and 5 sham stimulation sessions (n = 4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1 day, 1 month, and 3 months post stimulation. CSF samples were collected after each scan. Results Active aHF-rTMS significantly reduced striatal DAT BI 1 day post-active stimulation session (p < 0.01), and the effect lasted to 1 month (p < 0.01). No significant DAT BI change was found in sham group. No significant changes in dopamine metabolites of CSF were found. Conclusion Although no significant effects on CSF dopamine metabolites were observed, five sessions of active aHF-rTMS significantly decreased striatal DAT BI after 1 day and up to 1 month post stimulation, indicating immediate and delayed effects on the brain dopaminergic system. Our findings in healthy beagles further substantiate the assumption that (a)HF-rTMS affects the brain dopaminergic system and it may pave the way to apply (a)HF-rTMS treatment in behaviorally disturbed dogs.
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Affiliation(s)
- Yangfeng Xu
- Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Kathelijne Peremans
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Sofie Salden
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Kurt Audenaert
- Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium
| | - Andre Dobbeleir
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Ann Van Eeckhaut
- Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium
| | - Dimitri De Bundel
- Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium
| | - Jimmy H Saunders
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Chris Baeken
- Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium
- Department of Psychiatry, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel (UZBrussel), Brussels, Belgium
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands
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Xu Y, Christiaen E, De Witte S, Chen Q, Peremans K, Saunders JH, Vanhove C, Baeken C. Network analysis reveals abnormal functional brain circuitry in anxious dogs. PLoS One 2023; 18:e0282087. [PMID: 36920933 PMCID: PMC10016658 DOI: 10.1371/journal.pone.0282087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 02/07/2023] [Indexed: 03/16/2023] Open
Abstract
Anxiety is a common disease within human psychiatric disorders and has also been described as a frequently neuropsychiatric problem in dogs. Human neuroimaging studies showed abnormal functional brain networks might be involved in anxiety. In this study, we expected similar changes in network topology are also present in dogs. We performed resting-state functional MRI on 25 healthy dogs and 13 patients. The generic Canine Behavioral Assessment & Research Questionnaire was used to evaluate anxiety symptoms. We constructed functional brain networks and used graph theory to compare the differences between two groups. No significant differences in global network topology were found. However, focusing on the anxiety circuit, global efficiency and local efficiency were significantly higher, and characteristic path length was significantly lower in the amygdala in patients. We detected higher connectivity between amygdala-hippocampus, amygdala-mesencephalon, amygdala-thalamus, frontal lobe-hippocampus, frontal lobe-thalamus, and hippocampus-thalamus, all part of the anxiety circuit. Moreover, correlations between network metrics and anxiety symptoms were significant. Altered network measures in the amygdala were correlated with stranger-directed fear and excitability; altered degree in the hippocampus was related to attachment/attention seeking, trainability, and touch sensitivity; abnormal frontal lobe function was related to chasing and familiar dog aggression; attachment/attention seeking was correlated with functional connectivity between amygdala-hippocampus and amygdala-thalamus; familiar dog aggression was related to global network topology change. These findings may shed light on the aberrant topological organization of functional brain networks underlying anxiety in dogs.
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Affiliation(s)
- Yangfeng Xu
- Ghent Experimental Psychiatry (GHEP) Lab, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - Emma Christiaen
- Medical Image and Signal Processing (MEDISIP), Department of Electronics and Information Systems, Faculty of Engineering and Architecture, Ghent University, Ghent, Belgium
| | - Sara De Witte
- Ghent Experimental Psychiatry (GHEP) Lab, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Qinyuan Chen
- Ghent Experimental Psychiatry (GHEP) Lab, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Kathelijne Peremans
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - Jimmy H. Saunders
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium
| | - Christian Vanhove
- Medical Image and Signal Processing (MEDISIP), Department of Electronics and Information Systems, Faculty of Engineering and Architecture, Ghent University, Ghent, Belgium
| | - Chris Baeken
- Ghent Experimental Psychiatry (GHEP) Lab, Department of Head and Skin, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
- Department of Psychiatry, Faculty of Medicine and Pharmacy, Vrije University Brussels, Brussels, Belgium
- Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
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A Preliminary Study on the Interplay between the Serum Levels of Neurotransmitters and Thyroid Hormones for the Evaluation of the Behavioral Phenotype of Dogs. Animals (Basel) 2023; 13:ani13030411. [PMID: 36766302 PMCID: PMC9913781 DOI: 10.3390/ani13030411] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 01/23/2023] [Accepted: 01/25/2023] [Indexed: 01/28/2023] Open
Abstract
A total of 112 dogs (49 males and 63 females) belonging to different breeds (i.e., Boxer, Cirneco dell'Etna, Fonni's Dog, Labrador, Crossbreed, German Shepherd, Pit Bull, Shar-Pei, Yorkshire) were analyzed to compare the serum concentration of serotonin, dopamine, norepinephrine, prolactin, beta-endorphins, thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), and assess whether these parameters can be correlated with the behavioral phenotype of the investigated breeds. T4 was above or below the threshold in 61% and 14% of dogs, respectively; T3, in contrast, 41% of dogs showed values below the limit, while 26% above it. TSH was within the reference range in 58% of dogs; 94% of the dogs had prolactin in the reference range and only five animals showed values above the limit. For beta-endorphins, 49% of dogs had values above the limit, while 46% had values within the reference range. Serotonin and dopamine values below physiological limits were found in 62% and 70% of dogs, respectively. Finally, 61% of the dogs showed norepinephrine values within the reference range. The study confirmed that the assessment of the serum values of hormones and neurotransmitters in dogs could be useful to better understand the behavioral phenotype of the animal and could be useful for breeders and trainers for the selection of the most suitable subjects for specific tasks.
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Ghanbarzehi A, Sepehrinezhad A, Hashemi N, Karimi M, Shahbazi A. Disclosing common biological signatures and predicting new therapeutic targets in schizophrenia and obsessive-compulsive disorder by integrated bioinformatics analysis. BMC Psychiatry 2023; 23:40. [PMID: 36641432 PMCID: PMC9840830 DOI: 10.1186/s12888-023-04543-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Schizophrenia (SCZ) is a severe mental illness mainly characterized by a number of psychiatric symptoms. Obsessive-compulsive disorder (OCD) is a long-lasting and devastating mental disorder. SCZ has high co-occurrence with OCD resulting in the emergence of a concept entitled "schizo-obsessive disorder" as a new specific clinical entity with more severe psychiatric symptoms. Many studies have been done on SCZ and OCD, but the common pathogenesis between them is not clear yet. Therefore, this study aimed to identify shared genetic basis, potential biomarkers and therapeutic targets between these two disorders. Gene sets were extracted from the Geneweaver and Harmonizome databases for each disorder. Interestingly, the combination of both sets revealed 89 common genes between SCZ and OCD, the most important of which were BDNF, SLC6A4, GAD1, HTR2A, GRIN2B, DRD2, SLC6A3, COMT, TH and DLG4. Then, we conducted a comprehensive bioinformatics analysis of the common genes. Receptor activity as the molecular functions, neuron projection and synapse as the cellular components as well as serotonergic synapse, dopaminergic synapse and alcoholism as the pathways were the most significant commonalities in enrichment analyses. In addition, transcription factor (TFs) analysis predicted significant TFs such as HMGA1, MAPK14, HINFP and TEAD2. Hsa-miR-3121-3p and hsa-miR-495-3p were the most important microRNAs (miRNAs) associated with both disorders. Finally, our study predicted 19 existing drugs (importantly, Haloperidol, Fluoxetine and Melatonin) that may have a potential influence on this co-occurrence. To summarize, this study may help us to better understand and handle the co-occurrence of SCZ and OCD by identifying potential biomarkers and therapeutic targets.
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Affiliation(s)
- Abdolhakim Ghanbarzehi
- Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Sepehrinezhad
- Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nazanin Hashemi
- Department of Biotechnology, Bangalore University, Bangalore, Karnataka, India
| | - Minoo Karimi
- Department of Audiology, School of Rehabilitation, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Shahbazi
- Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Martín-González E, Olmedo-Córdoba M, Flores P, Moreno-Montoya M. Differential Neurobiological Markers in Phenotype-stratified Rats Modeling High or Low Vulnerability to Compulsive Behavior: A Narrative Review. Curr Neuropharmacol 2023; 21:1924-1933. [PMID: 36411566 PMCID: PMC10514532 DOI: 10.2174/1570159x21666221121091454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 09/15/2022] [Accepted: 10/31/2022] [Indexed: 11/23/2022] Open
Abstract
Compulsivity is a key manifestation of inhibitory control deficit and a cardinal symptom in different neuropsychopathological disorders such as obsessive-compulsive disorder, schizophrenia, addiction, and attention-deficit hyperactivity disorder. Schedule-induced polydipsia (SIP), is an animal model to study compulsivity. In this procedure, rodents develop excessive and persistent drinking behavior under different food-reinforcement schedules, that are not related to homeostatic or regulatory requirements. However, there are important individual differences that support the role of high-drinker HD rats as a compulsive phenotype, characterized in different paradigms by inhibitory response deficit, cognitive inflexibility, and resistant to extinction behavior; with significant differences in response to pharmacological challenges, and relevant neurobiological alterations in comparison with the control group, the non-compulsive low drinker LD group on SIP. The purpose of this review is to collate and update the main findings on the neurobiological bases of compulsivity using the SIP model. Specifically, we reviewed preclinical studies on SIP, that have assessed the effects of serotonergic, dopaminergic, and glutamatergic drugs; leading to the description of the neurobiological markers, such as the key role of the serotonin 5-HT2A receptor and glutamatergic signaling in a phenotype vulnerable to compulsivity as high drinker HD rats selected by SIP. The review of the main findings of HD rats on SIP helps in the characterization of the preclinical compulsive phenotype, disentangles the underlying neurobiological, and points toward genetic hallmarks concerning the vulnerability to compulsivity.
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Affiliation(s)
- Elena Martín-González
- Department of Psychology and Health Research Center (CEINSA), University of Almería, Almeria, Spain
| | - Manuela Olmedo-Córdoba
- Department of Psychology and Health Research Center (CEINSA), University of Almería, Almeria, Spain
| | - Pilar Flores
- Department of Psychology and Health Research Center (CEINSA), University of Almería, Almeria, Spain
| | - Margarita Moreno-Montoya
- Department of Psychology and Health Research Center (CEINSA), University of Almería, Almeria, Spain
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Aggressiveness, ADHD-like behaviour, and environment influence repetitive behaviour in dogs. Sci Rep 2022; 12:3520. [PMID: 35332179 PMCID: PMC8948230 DOI: 10.1038/s41598-022-07443-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 02/17/2022] [Indexed: 11/22/2022] Open
Abstract
Repetitive behaviour ranges from variants of normal repetitive behaviours to abnormal repetitive behaviours. The domestic dog spontaneously performs different repetitive behaviours, which can be severe and impair the quality of life and the dog-owner relationship. We collected comprehensive behavioural questionnaire data from almost 4500 Finnish pet dogs and studied the effect of several demographic, environmental, and behavioural factors on canine repetitive behaviour with logistic regression. We replicated findings from previous studies by revealing comorbidity between repetitive behaviour and behavioural factors aggressiveness, hyperactivity/impulsivity, and inattention. We also found a novel association between repetitive behaviour and the owner’s dog experience. In addition, we showed that repetitive behaviour is more common in dogs that live without conspecifics, dogs that were given a low amount of exercise, dogs that lived in larger families, young dogs and elderly dogs, and neutered dogs. Finally, we identified breed differences in repetitive behaviour, suggesting that some breeds are more vulnerable to repetitive behaviour and indicate a genetic susceptibility. As abnormal repetitive behaviour can considerably worsen the well-being of dogs and impair the dog-owner relationship, a better understanding of the environmental, lifestyle, and molecular factors affecting canine repetitive behaviour can benefit both dogs and humans.
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Benítez-Burraco A, Pörtl D, Jung C. Did Dog Domestication Contribute to Language Evolution? Front Psychol 2021; 12:695116. [PMID: 34589022 PMCID: PMC8473740 DOI: 10.3389/fpsyg.2021.695116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 08/02/2021] [Indexed: 11/20/2022] Open
Abstract
Different factors seemingly account for the emergence of present-day languages in our species. Human self-domestication has been recently invoked as one important force favoring language complexity mostly via a cultural mechanism. Because our self-domestication ultimately resulted from selection for less aggressive behavior and increased prosocial behavior, any evolutionary or cultural change impacting on aggression levels is expected to have fostered this process. Here, we hypothesize about a parallel domestication of humans and dogs, and more specifically, about a positive effect of our interaction with dogs on human self-domestication, and ultimately, on aspects of language evolution, through the mechanisms involved in the control of aggression. We review evidence of diverse sort (ethological mostly, but also archeological, genetic, and physiological) supporting such an effect and propose some ways of testing our hypothesis.
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Affiliation(s)
- Antonio Benítez-Burraco
- Department of Spanish, Linguistics, and Theory of Literature (Linguistics), Faculty of Philology, University of Seville, Seville, Spain
| | - Daniela Pörtl
- Psychiatric Department, Saale-Unstrut Klinikum, Teaching Hospital Leipzig and Jena Universities, Naumburg, Germany
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The Influence of Breed, Sex, Origin and Housing Conditions on Undesirable Behaviors in Ancient Dog Breeds. Animals (Basel) 2021; 11:ani11051435. [PMID: 34067911 PMCID: PMC8156398 DOI: 10.3390/ani11051435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/12/2021] [Accepted: 05/14/2021] [Indexed: 11/25/2022] Open
Abstract
Simple Summary Abnormal, repetitive behaviors often pose a problem for dog owners. Such behaviors are considered undesirable if they pose a nuisance or a danger to humans. This study aimed to identify factors (breed, sex, origin, housing conditions) and situations that contribute to undesirable behaviors, such as aggression towards humans and other dogs/animals, separation anxiety, excessive vocalization, and oral and locomotion behaviors in the ancient dog breeds Akita, Alaskan Malamute, Basenji, Samoyed and Siberian husky. Undesirable behaviors were analyzed based on the results of a survey involving dog owners. Undesirable behaviors were most frequently reported in Akitas, Siberian huskies and Samoyeds, and they were more prevalent in males than in females and dogs living indoors with or without access to a backyard. Aggressive behaviors towards other dogs and animals, excessive vocalization and undesirable motor activities posed the greatest problems in ancient dog breeds. Abstract Abnormal repetitive behaviors often pose problems for dog owners. Such behaviors are considered undesirable if they pose a nuisance or a danger to humans. Ancient dog breeds are intelligent, sociable, active, boisterous and need regular outdoor exercise, but are also independent and reluctant to follow commands. This study aimed to identify factors (breed, sex, origin, housing conditions) and situations that contribute to undesirable behaviors, such as aggression towards humans and other dogs/animals, separation anxiety, excessive vocalization, and oral and locomotion behaviors in Akita, Alaskan Malamute, Basenji, Samoyed and Siberian husky. Undesirable behaviors in dogs were analyzed based on the results of 897 questionnaires. Breed influenced aggressive behavior towards other dogs/animals, aggression towards humans, undesirable oral and locomotion behaviors, and excessive vocalization. Aggressive behaviors were more prevalent in females than in males. Housing conditions were linked with aggression towards other dogs/animals, aggression at mealtime, and excessive vocalization. Undesirable behaviors were most frequently reported in Akitas, Siberian huskies and Samoyeds, and they were more prevalent in males than in females and dogs living indoors with or without access to a backyard. Aggressive behaviors towards other dogs and animals, excessive vocalization and undesirable motor activities posed the greatest problems in ancient dog breeds.
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Kitchenham L, Mason GJ. The neurobiology of environmentally induced stereotypic behaviours in captive animals: assessing the basal ganglia pathways and cortico-striatal-thalamo-cortical circuitry hypotheses. BEHAVIOUR 2021. [DOI: 10.1163/1568539x-bja10084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Abstract
The neurobiology of environmentally induced stereotypic behaviours (SBs) (e.g., pacing in zoo carnivores, crib-biting in horses, tail chasing in dogs) is hypothesized to involve altered functioning within the basal ganglia (‘Basal Ganglia (BG) Pathways Hypotheses’) and/or between the basal ganglia and cortex (‘Cortico-Striatal-Thalamo-Cortical (CSTC) Circuits Hypotheses’). We review four decades of relevant studies, critically assessing support for both hypotheses. Currently no BG Pathways or CSTC Circuits hypothesis is fully supported. While some results are partially consistent with some hypotheses (decreased subthalamic nucleus activity in deer mice and C58 mice); others (nucleus accumbens activity in mink and C57 mice) seem to reflect individual differences in SB, but not environmental effects. Yet others can be tentatively rejected: neither elevated striatal dopamine nor the cortico-striatal connection of the sensorimotor circuit seem to be involved for most species studied to date. Further research is now important for understanding the impact of captivity on animals’ functioning.
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Affiliation(s)
- Lindsey Kitchenham
- Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada
| | - Georgia J. Mason
- Department of Integrative Biology, University of Guelph, Guelph, ON, Canada
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13
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Cao X, Liu WP, Cheng LG, Li HJ, Wu H, Liu YH, Chen C, Xiao X, Li M, Wang GD, Zhang YP. Whole genome analyses reveal significant convergence in obsessive-compulsive disorder between humans and dogs. Sci Bull (Beijing) 2021; 66:187-196. [PMID: 36654227 DOI: 10.1016/j.scib.2020.09.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 08/20/2020] [Accepted: 08/31/2020] [Indexed: 01/20/2023]
Abstract
Obsessive-compulsive disorder (OCD) represents a heterogeneous collection of diseases with diverse levels of phenotypic, genetic, and etiologic variability, making it difficult to identify the underlying genetic and biological mechanisms in humans. Domestic dogs exhibit several OCD-like behaviors. Using continuous circling as a representative phenotype for OCD, we screened two independent dog breeds, the Belgian Malinois and Kunming Dog and subsequently sequenced ten circling dogs and ten unaffected dogs for each breed. Using population differentiation analyses, we identified 11 candidate genes in the extreme tail of the differentiated regions between cases and controls. These genes overlap significantly with genes identified in a genome wide association study (GWAS) of human OCD, indicating strong convergence between humans and dogs. Through gene expressional analysis and functional exploration, we found that two candidate OCD risk genes, PPP2R2B and ADAMTSL3, affected the density and morphology of dendritic spines. Therefore, changes in dendritic spine may underlie some common biological and physiological pathways shared between humans and dogs. Our study revealed an unprecedented level of convergence in OCD shared between humans and dogs, and highlighted the importance of using domestic dogs as a model species for many human diseases including OCD.
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Affiliation(s)
- Xue Cao
- State Key Laboratory of Genetic Resources and Evolution and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Department of Laboratory Animal Science, Kunming Medical University, Kunming 650500, China
| | - Wei-Peng Liu
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650223, China
| | - Lu-Guang Cheng
- Kunming Police Dog Base, Ministry of Public Security, Kunming 650204, China
| | - Hui-Juan Li
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650223, China
| | - Hong Wu
- Laboratory for Conservation and Utilization of Bio-resource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming 650091, China
| | - Yan-Hu Liu
- State Key Laboratory of Genetic Resources and Evolution and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Chao Chen
- Kunming Police Dog Base, Ministry of Public Security, Kunming 650204, China
| | - Xiao Xiao
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
| | - Ming Li
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650223, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
| | - Guo-Dong Wang
- State Key Laboratory of Genetic Resources and Evolution and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.
| | - Ya-Ping Zhang
- State Key Laboratory of Genetic Resources and Evolution and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.
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14
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Walsh BR. A critical review of the evidence for the equivalence of canine and human compulsions. Appl Anim Behav Sci 2021. [DOI: 10.1016/j.applanim.2020.105166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Mora S, Merchán A, Aznar S, Flores P, Moreno M. Increased amygdala and decreased hippocampus volume after schedule-induced polydipsia in high drinker compulsive rats. Behav Brain Res 2020; 390:112592. [PMID: 32417273 DOI: 10.1016/j.bbr.2020.112592] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 02/04/2020] [Accepted: 02/25/2020] [Indexed: 02/08/2023]
Abstract
Fronto-limbic structures and serotonin 2A receptors (5-HT2A) have been implicated in the pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced Polydipsia (SIP), characterized by the development of excessive drinking under intermittent food reinforcement schedules, is a valid preclinical model for studying the compulsive phenotype. In the present study, we explored the individual differences and effect of SIP in brain volume and 5-HT2A receptor binding in fronto-limbic structures in rats selected according to their compulsive drinking behavior. Rats were divided into high (HD) and low drinkers (LD) by SIP (20 sessions); later, we analyzed the brains of HD and LD selected rats, in two different conditions: non-re-exposure (NRE) or re-exposure to SIP (RE), with four groups: LD-NRE, LD-RE, HD-NRE and HD-RE. Histological analyses were carried out for volumetric (stereology) and receptor binding (autoradiography) in the prelimbic and infralimbic cortex, dorsal hippocampus and basolateral amygdala. After SIP re-exposure, HD-RE showed an increased basolateral amygdala and a reduced hippocampus volume compared to HD-NRE rats, and also compared to LD-RE rats. No differences were found between HD and LD in NRE condition. Moreover, HD rats exhibit a lower 5-HT2A receptor binding in the basolateral amygdala, independently of SIP re-exposure, compared to LD rats. However, LD-RE showed a decreased 5-HT2A receptor binding in basolateral amygdala compared to LD-NRE. No differences were found in the remaining structures. These findings suggest that SIP might be differentially impacting HD and LD brains, pointing towards a possible explanation of how the latent vulnerability to compulsivity is triggered.
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Affiliation(s)
- Santiago Mora
- Department of Psychology & Health Research Centre (CEINSA), University of Almería, Almería, Spain
| | - Ana Merchán
- Department of Psychology & Health Research Centre (CEINSA), University of Almería, Almería, Spain
| | - Susana Aznar
- Research Laboratory for Stereology and Neuroscience, Bispebjerg-Frederiksberg University Hospital, Copenhagen, Denmark
| | - Pilar Flores
- Department of Psychology & Health Research Centre (CEINSA), University of Almería, Almería, Spain
| | - Margarita Moreno
- Department of Psychology & Health Research Centre (CEINSA), University of Almería, Almería, Spain.
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Rayment DJ, Peters RA, Marston LC, De Groef B. Relationships between serum serotonin, plasma cortisol, and behavioral factors in a mixed-breed, -sex, and -age group of pet dogs. J Vet Behav 2020. [DOI: 10.1016/j.jveb.2020.05.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Derksen M, Feenstra M, Willuhn I, Denys D. The serotonergic system in obsessive-compulsive disorder. HANDBOOK OF BEHAVIORAL NEUROSCIENCE 2020. [DOI: 10.1016/b978-0-444-64125-0.00044-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Pauwelyn G, Vlerick L, Dockx R, Verhoeven J, Dobbeleir A, Bosmans T, Peremans K, Vanhove C, Polis I, De Vos F. Kinetic analysis of [ 18F] altanserin bolus injection in the canine brain using PET imaging. BMC Vet Res 2019; 15:415. [PMID: 31752848 PMCID: PMC6873736 DOI: 10.1186/s12917-019-2165-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 11/06/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Currently, [18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. RESULTS The distribution of [18F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. CONCLUSIONS This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5-HT2A receptor in the canine brain.
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Affiliation(s)
- Glenn Pauwelyn
- Laboratory of Radiopharmacy, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
| | - Lise Vlerick
- Small animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Robrecht Dockx
- Small animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.,Department of Psychiatry and Medical Psychology, Ghent University, Ghent, Belgium
| | - Jeroen Verhoeven
- Laboratory of Radiopharmacy, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
| | - Andre Dobbeleir
- Small animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.,Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
| | - Tim Bosmans
- Small animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Kathelijne Peremans
- Small animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Christian Vanhove
- Institute Biomedical Technology - Medisip - Infinity, Ghent University, Ghent, Belgium
| | - Ingeborgh Polis
- Small animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Filip De Vos
- Laboratory of Radiopharmacy, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium
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Wolmarans DW, Stein DJ, Harvey BH. A Psycho-Behavioral Perspective on Modelling Obsessive-Compulsive Disorder (OCD) in Animals: The Role of Context. Curr Med Chem 2019; 25:5662-5689. [PMID: 28545371 DOI: 10.2174/0929867324666170523125256] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Revised: 04/18/2017] [Accepted: 05/29/2017] [Indexed: 01/24/2023]
Abstract
Obsessive-compulsive disorder is a heterogeneous and debilitating condition, characterized by intrusive thoughts and compulsive repetition. Animal models of OCD are important tools that have the potential to contribute significantly to our understanding of the condition. Although there is consensus that pre-clinical models are valuable in elucidating the underlying neurobiology in psychiatric disorders, the current paper attempts to prompt ideas on how interpretation of animal behavior can be expanded upon to more effectively converge with the human disorder. Successful outcomes in psychopharmacology involve rational design and synthesis of novel compounds and their testing in well-designed animal models. As part of a special journal issue on OCD, this paper will 1) review the psychobehavioral aspects of OCD that are of importance on how the above ideas can be articulated, 2) briefly elaborate on general issues that are important for the development of animal models of OCD, with a particular focus on the role and importance of context, 3) propose why translational progress may often be less than ideal, 4) highlight some of the significant contributions afforded by animal models to advance understanding, and 5) conclude by identifying novel behavioral constructs for future investigations that may contribute to the face, predictive and construct validity of OCD animal models. We base these targets on an integrative approach to face and construct validity, and note that the issue of treatment-resistance in the clinical context should receive attention in current animal models of OCD.
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Affiliation(s)
- De Wet Wolmarans
- Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North West-University, Potchefstroom, South Africa
| | - Dan J Stein
- MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.,Department of Psychiatry and Mental Health, MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa
| | - Brian H Harvey
- Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North West-University, Potchefstroom, South Africa.,MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa
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20
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Pauwelyn G, Vlerick L, Dockx R, Verhoeven J, Dobbeleir A, Peremans K, Goethals I, Bosmans T, Vanhove C, De Vos F, Polis I. PET quantification of [18F]MPPF in the canine brain using blood input and reference tissue modelling. PLoS One 2019; 14:e0218237. [PMID: 31185062 PMCID: PMC6559658 DOI: 10.1371/journal.pone.0218237] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 05/30/2019] [Indexed: 12/04/2022] Open
Abstract
Numerous studies have shown that the serotonin1A (5-HT1A) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2´-Methoxyphenyl)-1-[2´-(N-2´´-pyridinyl)-p- [18F]fluorobenzamidoethylpiperazine ([18F]MPPF) is a valid and useful PET tracer to visualize the 5HT1A receptor. However, to our knowledge, [18F]MPPF has never been demonstrated in the canine brain. The ability to image the 5HT1A receptor with PET in dogs could improve diagnosis and therapy in both canine and human behavioural and neuropsychiatric disorders. To examine the potential use of [18F]MPPF in dogs, five healthy adult laboratory beagles underwent a 60-minutes dynamic PET scan with [18F]MPPF while arterial blood samples were taken. For each region of interest, total distribution volume (VT) and corresponding binding potential (BPND) were calculated using the 1-tissue compartment model (1-TC), 2-Tissue compartment model (2-TC) and Logan plot. The preferred model was chosen based on the goodness-of-fit, calculated with the Akaike information criterium (AIC). Subsequently, the BPND values of the preferred compartment model were compared with the estimated BPND values using three reference tissue models (RTMs): the 2-step simplified reference tissue model (SRTM2), the 2-parameter multilinear reference tissue model (MRTM2) and the Logan reference tissue model. According to the lower AIC values of the 2-TC model compared to the 1-TC in all ROIs, the 2-TC model showed a better fit. Calculating BPND using reference tissue modelling demonstrated high correlation with the BPND obtained by metabolite corrected plasma input 2-TC. This first-in-dog study indicates the results of a bolus injection with [18F]MPPF in dogs are consistent with the observations presented in the literature for other animal species and humans. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region.
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Affiliation(s)
- Glenn Pauwelyn
- Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium
| | - Lise Vlerick
- Small Animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Robrecht Dockx
- Small Animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- Department of Psychiatry and Medical Psychology, Ghent University, Ghent, Belgium
| | | | - Andre Dobbeleir
- Small Animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
| | - Kathelijne Peremans
- Small Animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Ingeborg Goethals
- Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
| | - Tim Bosmans
- Small Animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Christian Vanhove
- Institute Biomedical Technology–Medisip–Infinity, Ghent University, Ghent, Belgium
| | - Filip De Vos
- Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium
| | - Ingeborgh Polis
- Small Animal Departments, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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21
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Cortical motor threshold determination in dogs. Res Vet Sci 2019; 124:248-255. [PMID: 30953941 DOI: 10.1016/j.rvsc.2019.03.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 03/26/2019] [Accepted: 03/29/2019] [Indexed: 11/23/2022]
Abstract
In humans, determining the cortical motor threshold (CMT) is a critical step in successfully applying a transcranial magnetic stimulation (TMS) treatment. Stimulus intensity, safety and efficacy of a TMS treatment are dependent of the correct assessment of the CMT. Given that TMS in dogs could serve as a natural animal model, an accurate and reliable technique for the measurement of the CMT should be available for dogs. Using a visual descending staircase paradigm (Rossini paradigm), the CMT repeatability was assessed and compared to the electromyographic (EMG) variant. The influence of a HF-rTMS treatment on the CMT was examined. Subsequently, the CMT was measured under sedation and general anaesthesia. Finally, the coil-cortex distance was associated with the CMT, weight, age and gender. During one year the CMT was measured three times, during which it remained constant, although a higher CMT was measured (40% higher machine output) when using EMG (P-value < .001) and under general anaesthesia (P-value = .005). On average, a 40% and 12% higher machine output were registered. An aHF-rTMS protocol does not influence the CMT. Males have on average a 5.2 mm larger coil cortex distance and an 11.81% higher CMT. The CMT was positively linearly associated (P-value < .05) with the weight and age of the animals. Only within female subjects, a positive linear association was found between the CMT and the coil-cortex distance (P-value = .02). Using the visual Rossini paradigm, the CMT can be reliably used over time and during a TMS treatment. It has to be kept in mind that when using EMG or assessing the CMT under general anaesthesia, a higher CMT is to be expected. As in humans, every parameter that influences the coil-cortex distance may also influence the CMT.
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Vlerick L, Peremans K, Dockx R, Audenaert K, Baeken C, Saunders JH, Polis I. The long-term effects of single and repeated subanaesthetic ketamine administration on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. Psychiatry Res Neuroimaging 2019; 285:18-24. [PMID: 30716686 DOI: 10.1016/j.pscychresns.2019.01.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 01/15/2019] [Accepted: 01/15/2019] [Indexed: 12/13/2022]
Abstract
Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders. Consequently, the aim of the current placebo controlled study was to assess the long-term effects on cerebral perfusion of single and repeated subanaesthetic ketamine infusions in dogs. Twelve healthy, laboratory dogs were scanned at six different time points following single and repeated ketamine administration, using Single Photon Emission Computed Tomography with the radiotracer 99mTc-hexamethylpropylene amine oxime. We hypothesised that repeated infusions could lead to more prolonged perfusion alterations in brain regions critical for behaviour regulation. We found that repeated subanaesthetic ketamine administration did not result in more prolonged cerebral perfusion alterations compared to a single ketamine administration.
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Affiliation(s)
- Lise Vlerick
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium.
| | - Kathelijne Peremans
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
| | - Robrecht Dockx
- Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium; Department of Psychiatry, University Hospital (UZBrussel), Brussels, Belgium
| | - Kurt Audenaert
- Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium; Department of Psychiatry, University Hospital (UZBrussel), Brussels, Belgium
| | - Chris Baeken
- Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium; Department of Psychiatry, University Hospital (UZBrussel), Brussels, Belgium
| | - Jimmy H Saunders
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
| | - Ingeborgh Polis
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
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Vlerick L, Peremans K, Dockx R, Audenaert K, Baeken C, De Spiegeleer B, Saunders J, Polis I. The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT. PLoS One 2018; 13:e0209316. [PMID: 30562399 PMCID: PMC6298672 DOI: 10.1371/journal.pone.0209316] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 12/04/2018] [Indexed: 02/06/2023] Open
Abstract
Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine's antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer 99mTc-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine's beneficial effects in these psychiatric disorders.
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Affiliation(s)
- Lise Vlerick
- Department of Small Animal, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
| | - Kathelijne Peremans
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
| | - Robrecht Dockx
- Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium
| | - Kurt Audenaert
- Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium
| | - Chris Baeken
- Ghent Experimental Psychiatry (GHEP) lab, Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East Flanders, Belgium
| | - Bart De Spiegeleer
- Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, East Flanders, Belgium
| | - Jimmy Saunders
- Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
| | - Ingeborgh Polis
- Department of Small Animal, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
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Mora S, Merchán A, Vilchez O, Aznar S, Klein AB, Ultved L, Campa L, Suñol C, Flores P, Moreno M. Reduced cortical serotonin 5-HT2A receptor binding and glutamate activity in high compulsive drinker rats. Neuropharmacology 2018; 143:10-19. [DOI: 10.1016/j.neuropharm.2018.09.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 08/15/2018] [Accepted: 09/06/2018] [Indexed: 11/16/2022]
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Hwang M, Sood A, Riaz B, Poyurovsky M. Obsessive-Compulsive Schizophrenia: Clinical andConceptual Perspective. Psychiatr Ann 2018. [DOI: 10.3928/00485713-20181108-02] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Hrovat A, De Keuster T, Kooistra HS, Duchateau L, Oyama MA, Peremans K, Daminet S. Behavior in dogs with spontaneous hypothyroidism during treatment with levothyroxine. J Vet Intern Med 2018; 33:64-71. [PMID: 30499213 PMCID: PMC6335523 DOI: 10.1111/jvim.15342] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 10/15/2018] [Indexed: 11/27/2022] Open
Abstract
Background Thyroid hormone supplementation anecdotally has been described as a valid treatment option for dogs with aggression‐related problems. However, prospective, controlled, and blinded trials evaluating behavior and neurohormonal status in hypothyroid dogs during treatment with levothyroxine are lacking. Objective Levothyroxine supplementation will have a significant influence on the behavior and neurohormonal status of dogs with spontaneous hypothyroidism. Animals Twenty client‐owned dogs diagnosed with spontaneous hypothyroidism. Methods This prospective study was to evaluate the behavior of dogs, which was screened at initial presentation, and after 6 weeks, and 6 months of treatment with levothyroxine (starting dosage 10 μg/kg PO q12h) using the standardized Canine Behavioral Assessment and Research Questionnaire (C‐BARQ). At each time period, circulating serotonin and prolactin (PRL) concentrations were evaluated using a commercially validated ELISA kit and heterologous radioimmunoassay, respectively. Results After 6 weeks of thyroid hormone supplementation, C‐BARQ scores demonstrated a significant increase in activity of hypothyroid dogs (P < .01). No significant change in any of the behavioral signs was observed after 6 months of treatment. No significant difference in circulating concentrations of serotonin (P > .99 and P = .46) and PRL (P = .99 and P = .37) were noted between the 6‐week and 6‐month periods compared with baseline. Conclusions and Clinical Importance The results of this study indicate increased activity of hypothyroid dogs after 6 weeks of thyroid hormone supplementation. None of the hypothyroid dogs in this cohort showed a significant change in any of the evaluated behavioral signs and neurohormonal status after 6 months of thyroid hormone supplementation.
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Affiliation(s)
- Alenka Hrovat
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Tiny De Keuster
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Hans S Kooistra
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Luc Duchateau
- Biometrics Research Group, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Mark A Oyama
- Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kathelijne Peremans
- Department of Veterinary Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Sylvie Daminet
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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Wolmarans DW, Scheepers IM, Stein DJ, Harvey BH. Peromyscus maniculatus bairdii as a naturalistic mammalian model of obsessive-compulsive disorder: current status and future challenges. Metab Brain Dis 2018; 33:443-455. [PMID: 29214602 DOI: 10.1007/s11011-017-0161-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 11/23/2017] [Indexed: 10/18/2022]
Abstract
Obsessive-compulsive disorder (OCD) is a prevalent and debilitating condition, characterized by intrusive thoughts and repetitive behavior. Animal models of OCD arguably have the potential to contribute to our understanding of the condition. Deer mice (Permomyscus maniculatus bairdii) are characterized by stereotypic behavior which is reminiscent of OCD symptomology, and which may serve as a naturalistic animal model of this disorder. Moreover, a range of deer mouse repetitive behaviors may be representative of different compulsive-like phenotypes. This paper will review work on deer mouse behavior, and evaluate the extent to which this serves as a valid and useful model of OCD. We argue that findings over the past decade indicate that the deer mouse model has face, construct and predictive validity.
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Affiliation(s)
- De Wet Wolmarans
- Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Private Bag X6001, Potchefstroom, South Africa.
| | - Isabella M Scheepers
- Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Private Bag X6001, Potchefstroom, South Africa
| | - Dan J Stein
- MRC Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa
- Department of Psychiatry and Mental Health, MRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa
| | - Brian H Harvey
- Division of Pharmacology, Center of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Private Bag X6001, Potchefstroom, South Africa
- MRC Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa
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Using an owner-based questionnaire to phenotype dogs with separation-related distress: Do owners know what their dogs do when they are absent? J Vet Behav 2018. [DOI: 10.1016/j.jveb.2017.10.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Dockx R, Peremans K, Duprat R, Vlerick L, Van Laeken N, Saunders JH, Polis I, De Vos F, Baeken C. Accurate external localization of the left frontal cortex in dogs by using pointer based frameless neuronavigation. PeerJ 2017; 5:e3425. [PMID: 28713649 PMCID: PMC5507169 DOI: 10.7717/peerj.3425] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 05/16/2017] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND In humans, non-stereotactic frameless neuronavigation systems are used as a topographical tool for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS). TMS studies in dogs may provide treatment modalities for several neuropsychological disorders in dogs. Nevertheless, an accurate non-invasive localization of a stimulation target has not yet been performed in this species. HYPOTHESIS This study was primarily put forward to externally locate the left frontal cortex in 18 healthy dogs by means of a human non-stereotactic neuronavigation system. Secondly, the accuracy of the external localization was assessed. ANIMALS A total of 18 healthy dogs, drawn at random from the research colony present at the faculty of Veterinary Medicine (Ghent University), were used. METHODS Two sets of coordinates (X, Y, Z and X″, Y″, Z″) were compared on each dog their tomographical dataset. RESULTS The non-stereotactic neuronavigation system was able to externally locate the frontal cortex in dogs with accuracy comparable with human studies. CONCLUSION AND CLINICAL IMPORTANCE This result indicates that a non-stereotactic neuronavigation system can accurately externally locate the left frontal cortex and paves the way to use guided non-invasive brain stimulation methods as an alternative treatment procedure for neurological and behavioral disorders in dogs. This technique could, in analogy with human guided non-invasive brain stimulation, provide a better treatment outcome for dogs suffering from anxiety disorders when compared to its non-guided alternative.
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Affiliation(s)
- Robrecht Dockx
- Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East-Flanders, Belgium.,Faculty of Veterinary Medicine, Ghent University, Merelbeke, East-Flanders, Belgium
| | - Kathelijne Peremans
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, East-Flanders, Belgium
| | - Romain Duprat
- Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East-Flanders, Belgium
| | - Lise Vlerick
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, East-Flanders, Belgium
| | - Nick Van Laeken
- Faculty of Pharmaceutical Sciences, Ghent University, Ghent, East-Flanders, Belgium
| | - Jimmy H Saunders
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, East-Flanders, Belgium
| | - Ingeborgh Polis
- Faculty of Veterinary Medicine, Ghent University, Merelbeke, East-Flanders, Belgium
| | - Filip De Vos
- Faculty of Pharmaceutical Sciences, Ghent University, Ghent, East-Flanders, Belgium
| | - Chris Baeken
- Department of Psychiatry and Medical Psychology, Ghent University, Ghent, East-Flanders, Belgium
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Hall NJ. Persistence and resistance to extinction in the domestic dog: Basic research and applications to canine training. Behav Processes 2017; 141:67-74. [PMID: 28392243 DOI: 10.1016/j.beproc.2017.04.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Revised: 03/29/2017] [Accepted: 04/05/2017] [Indexed: 11/18/2022]
Abstract
This review summarizes the research investigating behavioral persistence and resistance to extinction in the dog. The first part of this paper reviews Behavioral Momentum Theory and its applications to Applied Behavior Analysis and training of pet dogs with persistent behavioral problems. I also highlight how research on Behavioral Momentum Theory can be applied to the training of detection dogs in an attempt to enhance detection performance in the presence of behavioral disruptors common in operational settings. In the second part of this review, I highlight more basic research on behavioral persistence with dogs, and how breed differences and experiences with humans as alternative sources of reinforcement can influence dogs' resistance to extinction of a target behavior. Applied Behavior Analysis and Behavior Momentum Theory have important applications for behavioral treatments to reduce the persistence of problem behavior in dogs and for the development of enhanced training methods that enhance the persistence of working dogs. Dogs can also be leveraged as natural models of stereotypic behavior and for exploring individual differences in behavioral persistence by evaluating breed and environmental variables associated with differences in canine persistance.
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Verstegen JP. Does diet contribute to abnormal dog behaviour? Vet Rec 2017; 180:16-17. [PMID: 28062775 DOI: 10.1136/vr.j52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- John P Verstegen
- College of Veterinary Medicine, University ofWisconsin, Madison, Wisconsin 53706, USA e-mail:
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Sechi S, Di Cerbo A, Canello S, Guidetti G, Chiavolelli F, Fiore F, Cocco R. Effects in dogs with behavioural disorders of a commercial nutraceutical diet on stress and neuroendocrine parameters. Vet Rec 2016; 180:18. [PMID: 27885066 PMCID: PMC5284471 DOI: 10.1136/vr.103865] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2016] [Indexed: 02/07/2023]
Abstract
The well-being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioural disorders including fear, hyperactivity and anxiety, followed by negative affective moods and poor welfare. This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioural disorders related to anxiety and chronic stress. They were fed a control diet or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, β-endorphins, noradrenaline and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP)) parameters related to behavioural disorders were evaluated at the beginning and end of the study period. Results showed a significant increase in serotonin, dopamine and β-endorphins plasma concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neuroendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and nutraceuticals in the treatment of behavioural disorders.
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Affiliation(s)
- S Sechi
- Department of Veterinary Medicine, Pathology and Veterinary Clinic Section, University of Sassari, Via Vienna 2, 07100 Sassari, Italy
| | - A Di Cerbo
- Department of Biomedical Sciences, School of Specialization in Clinical Biochemistry, "G. d'Annunzio" University, Via dei Vestini 31, 66100 Chieti, Italy
| | - S Canello
- Research and Development Department, Forza10 USA Corp., 10142 Canopy Tree Ct. 32836 Orlando, Florida, USA
| | - G Guidetti
- Research and Development Department, Forza10 USA Corp., 10142 Canopy Tree Ct. 32836 Orlando, Florida, USA
| | - F Chiavolelli
- Department of Diagnostic Medicine, Clinical and Public Health, University of Modena and Reggio Emilia, Via Campi 213/A, 41125 Modena, Italy
| | - F Fiore
- Department of Veterinary Medicine, Pathology and Veterinary Clinic Section, University of Sassari, Via Vienna 2, 07100 Sassari, Italy
| | - R Cocco
- Department of Veterinary Medicine, Pathology and Veterinary Clinic Section, University of Sassari, Via Vienna 2, 07100 Sassari, Italy
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Taylor O, Audenaert K, Baeken C, Saunders J, Peremans K. Nuclear medicine for the investigation of canine behavioral disorders. J Vet Behav 2016. [DOI: 10.1016/j.jveb.2016.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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34
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Overall KL, Dunham AE, Juarbe-Diaz SV. Phenotypic determination of noise reactivity in 3 breeds of working dogs: A cautionary tale of age, breed, behavioral assessment, and genetics. J Vet Behav 2016. [DOI: 10.1016/j.jveb.2016.09.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Ogata N. Separation anxiety in dogs: What progress has been made in our understanding of the most common behavioral problems in dogs? J Vet Behav 2016. [DOI: 10.1016/j.jveb.2016.02.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Dantas LMS. Animal Behavior Case of the Month. J Am Vet Med Assoc 2016; 249:747-50. [DOI: 10.2460/javma.249.7.747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Qiao H, Zhang Y, Wu Z, Zhu L, Choi SR, Ploessl K, Kung HF. One-step preparation of [(18)F]FPBM for PET imaging of serotonin transporter (SERT) in the brain. Nucl Med Biol 2016; 43:470-7. [PMID: 27236282 DOI: 10.1016/j.nucmedbio.2016.04.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 03/16/2016] [Accepted: 04/14/2016] [Indexed: 01/27/2023]
Abstract
Serotonin transporters (SERT) in the brain play an important role in normal brain function. Selective serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, escitalopram, etc., specifically target SERT binding in the brain. Development of SERT imaging agents may be useful for studying the function of SERT by in vivo imaging. A one-step preparation of [(18)F]FPBM, 2-(2'-(dimethylamino)methyl)-4'-(3-([(18)F]fluoropropoxy)phenylthio)benzenamine, for positron emission tomography (PET) imaging of SERT binding in the brain was achieved. An active OTs intermediate, 9, was reacted with [(18)F]F(-)/K222 to produce [(18)F]FPBM in one step and in high radiochemical yield. This labeling reaction was evaluated and optimized under different temperatures, bases, solvents, and varying amounts of precursor 9. The radiolabeling reaction led to the desired [(18)F]FPBM in one step and the crude product was purified by HPLC purification to give no-carrier-added [(18)F]FPBM (radiochemical yield, 24-33%, decay corrected; radiochemical purity >99%). PET imaging studies in normal monkeys (n=4) showed fast, pronounced uptakes in the midbrain and thalamus, regions known to be rich in SERT binding sites. A displacement experiment with escitalopram (5mg/kg iv injection at 30min after [(18)F]FPBM injection) showed a rapid and complete reversal of SERT binding, suggesting that binding by [(18)F]FPBM was highly specific and reversible. A one-step radiolabeling method coupled with HPLC purification for preparation of [(18)F]FPBM was developed. Imaging studies suggest that it is feasible to use this method to prepare [(18)F]FPBM for in vivo PET imaging of SERT binding in the brain.
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Affiliation(s)
- Hongwen Qiao
- Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Yan Zhang
- Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing, 100875, China
| | - Zehui Wu
- Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Lin Zhu
- Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China; Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing, 100875, China; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
| | - Seok Rye Choi
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Karl Ploessl
- Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Hank F Kung
- Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Dumas N, Moulin-Sallanon M, Fender P, Tournier BB, Ginovart N, Charnay Y, Millet P. In Vivo Quantification of 5-HT2A Brain Receptors in Mdr1a KO Rats with 123I-R91150 Single-Photon Emission Computed Tomography. Mol Imaging 2016; 14. [PMID: 26105563 DOI: 10.2310/7290.2015.00006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Our goal was to identify suitable image quantification methods to image 5-hydroxytryptamine2A (5-HT2A) receptors in vivo in Mdr1a knockout (KO) rats (i.e., P-glycoprotein KO) using 123I-R91150 single-photon emission computed tomography (SPECT). The 123I-R91150 binding parameters estimated with different reference tissue models (simplified reference tissue model [SRTM], Logan reference tissue model, and tissue ratio [TR] method) were compared to the estimates obtained with a comprehensive three-tissue/seven-parameter (3T/7k)-based model. The SRTM and Logan reference tissue model estimates of 5-HT2A receptor (5-HT2AR) nondisplaceable binding potential (BPND) correlated well with the absolute receptor density measured with the 3T/7k gold standard (r > .89). Quantification of 5-HT2AR using the Logan reference tissue model required at least 90 minutes of scanning, whereas the SRTM required at least 110 minutes. The TR method estimates were also highly correlated to the 5-HT2AR density (r > .91) and only required a single 20-minute scan between 100 and 120 minutes postinjection. However, a systematic overestimation of the BPND values was observed. The Logan reference tissue method is more convenient than the SRTM for the quantification of 5-HT2AR in Mdr1a KO rats using 123I-R91150 SPECT. The TR method is an interesting and simple alternative, despite its bias, as it still provides a valid index of 5-HT2AR density.
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Van Laeken N, Taylor O, Polis I, Neyt S, Kersemans K, Dobbeleir A, Saunders J, Goethals I, Peremans K, De Vos F. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain. PLoS One 2016; 11:e0148943. [PMID: 26859850 PMCID: PMC4747581 DOI: 10.1371/journal.pone.0148943] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 01/23/2016] [Indexed: 11/19/2022] Open
Abstract
This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs.
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Affiliation(s)
- Nick Van Laeken
- Department of Radiopharmacy, Ghent University, Ghent, Belgium
- * E-mail:
| | - Olivia Taylor
- Department of Medical Imaging and Small Animal Orthopedics, Ghent University, Ghent, Belgium
| | - Ingeborgh Polis
- Department of Medicine and Clinical Biology of Small Animals, Ghent University, Ghent, Belgium
| | - Sara Neyt
- Department of Radiopharmacy, Ghent University, Ghent, Belgium
| | - Ken Kersemans
- Department of Radiology and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
| | - Andre Dobbeleir
- Department of Radiology and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
| | - Jimmy Saunders
- Department of Medical Imaging and Small Animal Orthopedics, Ghent University, Ghent, Belgium
| | - Ingeborg Goethals
- Department of Radiology and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium
| | - Kathelijne Peremans
- Department of Medical Imaging and Small Animal Orthopedics, Ghent University, Ghent, Belgium
| | - Filip De Vos
- Department of Radiopharmacy, Ghent University, Ghent, Belgium
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Taylor O, Van Laeken N, De Vos F, Polis I, Bosmans T, Goethals I, Achten R, Dobbeleir A, Vandermeulen E, Baeken C, Saunders J, Peremans K. In vivo quantification of the [(11)C]DASB binding in the normal canine brain using positron emission tomography. BMC Vet Res 2015; 11:308. [PMID: 26704517 PMCID: PMC4690221 DOI: 10.1186/s12917-015-0622-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 12/18/2015] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) is currently the mostly used radiotracer for positron emission tomography (PET) quantitative studies of the serotonin transporter (SERT) in the human brain but has never been validated in dogs. The first objective was therefore to evaluate normal [(11)C]DASB distribution in different brain regions of healthy dogs using PET. The second objective was to provide less invasive and more convenient alternative methods to the arterial sampling-based kinetic analysis. RESULTS A dynamic acquisition of the brain was performed during 90 min. The PET images were coregistered with the magnetic resonance images taken prior to the study in order to manually drawn 20 regions of interest (ROIs). The highest radioactivity concentration of [(11)C]DASB was observed in the hypothalamus, raphe nuclei and thalamus and lowest levels in the parietal cortex, occipital cortex and cerebellum. The regional radioactivity in those 20 ROIs was quantified using the multilinear reference tissue model 2 (MRTM2) and a semi-quantitative method. The values showed least variability between 40 and 60 min and this time interval was set as the optimal time interval for [(11)C]DASB quantification in the canine brain. The correlation (R(2)) between the MRTM2 and the semi-quantitative method using the data between 40 and 60 min was 99.3% (two-tailed p-value < 0.01). CONCLUSIONS The reference tissue models and semi-quantitative method provide a more convenient alternative to invasive arterial sampling models in the evaluation of the SERT of the normal canine brain. The optimal time interval for static scanning is set at 40 to 60 min after tracer injection.
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Affiliation(s)
- Olivia Taylor
- Department of Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
| | - Nick Van Laeken
- Laboratory of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
| | - Filip De Vos
- Laboratory of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
| | - Ingeborgh Polis
- Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
| | - Tim Bosmans
- Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
| | - Ingeborg Goethals
- Department of Nuclear Medicine, Ghent University Hospital, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
| | - Rik Achten
- Department of Radiology, Ghent University Hospital, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
| | - Andre Dobbeleir
- Department of Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
- Department of Nuclear Medicine, Ghent University Hospital, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
| | - Eva Vandermeulen
- Department of Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
| | - Chris Baeken
- Department of Psychiatry and Medical Psychology, Ghent University Hospital, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
| | - Jimmy Saunders
- Department of Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
| | - Kathelijne Peremans
- Department of Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
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Comparison of owner-reported behavioral characteristics among genetically clustered breeds of dog (Canis familiaris). Sci Rep 2015; 5:17710. [PMID: 26680442 PMCID: PMC4683527 DOI: 10.1038/srep17710] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Accepted: 11/04/2015] [Indexed: 11/09/2022] Open
Abstract
During the domestication process, dogs were selected for their suitability for multiple purposes, resulting in a variety of behavioral characteristics. In particular, the ancient group of breeds that is genetically closer to wolves may show different behavioral characteristics when compared to other breed groups. Here, we used questionnaire evaluations of dog behavior to investigate whether behavioral characteristics of dogs were different among genetically clustered breed groups. A standardized questionnaire, the Canine Behavioral Assessment and Research Questionnaire (C-BARQ), was used, and breed group differences of privately-owned dogs from Japan (n = 2,951) and the United States (n = 10,389) were analyzed. Results indicated that dogs in the ancient and spitz breed group showed low attachment and attention-seeking behavior. This characteristic distinguished the ancient group from any other breed groups with presumed modern European origins, and may therefore, be an ancestral trait.
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Lower availability of striatal dopamine transporter in generalized anxiety disorder: a preliminary two-ligand SPECT study. Int Clin Psychopharmacol 2015; 30:175-8. [PMID: 25647452 DOI: 10.1097/yic.0000000000000067] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Dopamine and serotonin have been indirectly found to be associated with generalized anxiety disorder (GAD). The aims of this study were to examine the availabilities of the striatal dopamine transporter (DAT) and the midbrain serotonin transporter (SERT) in patients with GAD. 12 patients with GAD and 12 sex-matched, age-matched, and smoking status-matched healthy controls were recruited. The availabilities of DAT and SERT were approximated using single-photon emission computed tomography, with [Tc]TRODAT-1 and [I]ADAM as the ligands. There were several missing data for six participants with GAD in the ADAM study because of a lack of the radioligand at the time of the experiment. The DAT availability in the striatum was significantly lower in the patients with GAD than in the healthy controls. However, the SERT availability did not differ between the two groups. The results with respect to the striatal DAT level suggested a potential role in the pathophysiology of GAD.
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Navarro SV, Gutiérrez-Ferre V, Flores P, Moreno M. Activation of serotonin 5-HT2A receptors inhibits high compulsive drinking on schedule-induced polydipsia. Psychopharmacology (Berl) 2015; 232:683-97. [PMID: 25155310 DOI: 10.1007/s00213-014-3699-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Accepted: 07/28/2014] [Indexed: 11/26/2022]
Abstract
RATIONALE Schedule-induced polydipsia (SIP) is an established model for studying compulsive behaviour in rats. Serotoninergic drugs effectively reduce compulsive drinking on SIP, and high compulsive drinker rats selected by SIP have shown differences in serotoninergic brain activity. However, the specific serotoninergic receptors that modulate compulsive SIP remain unclear. OBJECTIVE We investigated the functional role of serotonin 5-hydroxytryptamine 2A or C (5-HT2A/C) receptors in compulsive SIP behaviour. METHODS Rats were selected for low (LD) versus high drinking (HD) behaviour on SIP. The effects of the systemic administration of the selective serotonin reuptake inhibitor citalopram, selective norepinephrine reuptake inhibitor atomoxetine, serotonin 5-HT2A/C receptor agonist DOI hydrochloride ((±)-2,5-dimethoxy-4-iodoamphetamine), serotonin 5-HT2C receptor antagonist SB242084, serotonin 5-HT2A receptor antagonist ketanserin and M100907 were assessed on SIP. Subsequently, the effects of DOI were tested after the pre-administration of SB242084, ketanserin and M100907 on SIP. RESULTS Citalopram and DOI reduced compulsive drinking in HD compared with LD rats on SIP. In contrast, SB242084 increased compulsive drinking in HD compared with LD rats on SIP. Atomoxetine, ketanserin and M100907 had no effect on SIP. The reduction in water intake produced by DOI was blocked by ketanserin and M100907, but not by SB242084 administration, in HD rats. CONCLUSIONS These findings highlight the contribution of serotoninergic 5-HT2A/C receptors compared with noradrenergic mechanisms on SIP and reveal the "therapeutic" activation of serotonin 5-HT2A in the inhibition of the compulsive drinking behaviour in HD rats. Thus, it may represent a potentially new marker of vulnerability and provides additional insight for potential treatments on compulsive behaviours in neuropsychiatric populations.
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Affiliation(s)
- Silvia Victoria Navarro
- Department of Psychology, University of Almería, Campus de Excelencia Internacional Agroalimentario CeiA3, Carretera de Sacramento s/n, 04120, Almería, Spain
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Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD). Psychopharmacology (Berl) 2014; 231:3707-18. [PMID: 24682503 DOI: 10.1007/s00213-014-3505-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 02/12/2014] [Indexed: 02/08/2023]
Abstract
RATIONALE Acute administration of serotonergic agonist, meta-chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in an animal model of obsessive-compulsive disorder (OCD). It is not known whether mCPP has a similar effect on development of compulsive checking. OBJECTIVES The objective of the study was to examine whether similar mechanisms mediate the development versus the performance of compulsive checking in the rat model. METHODS Four groups of male rats (N = 14/group) were tested: two experimental groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with quinpirole and saline, the other receiving injections of saline. The time course of development of compulsive checking across injections 1 to 10 in quinpirole-treated rats was compared to rats co-injected with quinpirole and mCPP. RESULTS Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg) significantly attenuated performance of checking behavior. However, when these rats were retested for expression of compulsive checking (that is, with an injection of quinpirole only), their profile of compulsive checking was no different from the control rats treated throughout with quinpirole only. CONCLUSIONS Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.
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Rigterink A, Houpt K. Genetics of canine behavior: A review. World J Med Genet 2014; 4:46-57. [DOI: 10.5496/wjmg.v4.i3.46] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Revised: 05/20/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
The past decade has seen rapid progress in the field of canid behavioral genetics. The recent advances are summarized in this review. The identification of the genes responsible for tameness in silver foxes is the culmination of a half century of behavioral testing and, more recently, genomic investigation. There is agreement that domestic dogs evolved from wolves, but when and from which population remains controversial. The genetic differences between wolves and dogs identified include those for neurotransmitters and digestion. Breed differences in behavior are well known, but only recently have the genetics underlying these differences been investigated. The genes responsible for flank sucking in Doberman Pinschers and for several other obsessive compulsive problems in other breeds have been identified. Aggression is the least desirable canine trait, and several laboratories have detected differences in neurotransmitters and their receptors between aggressive and non-aggressive dogs. In English Cocker Spaniels, the genes linked to aggressive behavior code for dopamine, serotonin, and glutamate receptors. A dopamine transporter gene has been associated with impulsive behavior in Malinois.
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Abstract
Veterinarians have gained increasing access to positron emission tomography (PET and PET/CT) imaging facilities, allowing them to use this powerful molecular imaging technique for clinical and research applications. SPECT is currently being used more in Europe than in the United States and has been shown to be useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate behavioral disorders in animals that have interesting similarities to human psychiatric disorders. This article provides an overview of the potential applications of PET and SPECT. The use of commercially available and investigational PET radiopharmaceuticals in the management of veterinary disease has been discussed. To date, most of the work in this field has utilized the commercially available PET tracer, (18)F-fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and birds) have been published to assist in lesion detection and interpretation for veterinary radiologists and clinicians. Studies evaluating other (18)F-labeled tracers for research applications are underway at several institutions and companion animal models of human diseases are being increasingly recognized for their value in biomarker and therapy development. Although PET and SPECT technologies are in their infancy for clinical veterinary medicine, increasing access to and interest in these applications and other molecular imaging techniques has led to a greater knowledge and collective body of expertise for veterinarians worldwide. Initiation and fostering of physician-veterinarian collaborations are key components to the forward movement of this field.
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Affiliation(s)
- Amy K LeBlanc
- Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Veterinary Teaching Hospital, Knoxville, TN.
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Abstract
Obsessive-compulsive disorder (OCD) and related conditions (trichotillomania, pathological skin-picking, pathological nail-biting) are common and disabling. Current treatment approaches fail to help a significant proportion of patients. Multiple tiers of evidence link these conditions with underlying dysregulation of particular cortico-subcortical circuitry and monoamine systems, which represent targets for treatment. Animal models designed to capture aspects of these conditions are critical for several reasons. First, they help in furthering our understanding of neuroanatomical and neurochemical underpinnings of the obsessive-compulsive (OC) spectrum. Second, they help to account for the brain mechanisms by which existing treatments (pharmacotherapy, psychotherapy, deep brain stimulation) exert their beneficial effects on patients. Third, they inform the search for novel treatments. This article provides a critique of key animal models for selected OC spectrum disorders, beginning with initial work relating to anxiety, but moving on to recent developments in domains of genetic, pharmacological, cognitive, and ethological models. We find that there is a burgeoning literature in these areas with important ramifications, which are considered, along with salient future lines of research.
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Klanker M, Feenstra M, Denys D. Dopaminergic control of cognitive flexibility in humans and animals. Front Neurosci 2013; 7:201. [PMID: 24204329 PMCID: PMC3817373 DOI: 10.3389/fnins.2013.00201] [Citation(s) in RCA: 162] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2013] [Accepted: 10/11/2013] [Indexed: 12/21/2022] Open
Abstract
Striatal dopamine (DA) is thought to code for learned associations between cues and reinforcers and to mediate approach behavior toward a reward. Less is known about the contribution of DA to cognitive flexibility—the ability to adapt behavior in response to changes in the environment. Altered reward processing and impairments in cognitive flexibility are observed in psychiatric disorders such as obsessive compulsive disorder (OCD). Patients with this disorder show a disruption of functioning in the frontostriatal circuit and alterations in DA signaling. In this review we summarize findings from animal and human studies that have investigated the involvement of striatal DA in cognitive flexibility. These findings may provide a better understanding of the role of dopaminergic dysfunction in cognitive inflexibility in psychiatric disorders, such as OCD.
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Affiliation(s)
- Marianne Klanker
- Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences Amsterdam, Netherlands ; Department of Psychiatry, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands
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Zhu L, Li G, Choi SR, Plössl K, Chan P, Qiao H, Zha Z, Kung HF. An improved preparation of [18F]FPBM: A potential serotonin transporter (SERT) imaging agent. Nucl Med Biol 2013; 40:974-9. [DOI: 10.1016/j.nucmedbio.2013.08.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2013] [Accepted: 08/04/2013] [Indexed: 10/26/2022]
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