title: Serotonin 2A receptor, serotonin transporter and dopamine transporter alterations in dogs with compulsive behaviour as a promising model for human obsessive-compulsive disorder.
abstract: Neuro-imaging studies have shown altered, yet often inconsistent, serotonergic and dopaminergic neurotransmission in patients with obsessive-compulsive disorder (OCD). We investigated both serotonergic and dopaminergic neurotransmission in 9 drug-naïve dogs with compulsive behaviour, as a potential model for human OCD. Single photon emission computed tomography was used with (123)I-R91150 and (123)I-FP-CIT, in combination with (99m)Tc-ECD brain perfusion co-registration, to measure the serotonin (5-HT) 2A receptor, dopamine transporter (DAT) and serotonin transporter (SERT) availability. Fifteen normally behaving dogs were used as reference group. Significantly lower 5-HT2A receptor radioligand availability in frontal and temporal cortices (bilateral) was observed. Further, in 78% of the compulsive dogs abnormal DAT ratios in left and right striatum were demonstrated. Interestingly, both increased and decreased DAT ratios were observed. Finally, significantly lower subcortical perfusion and (hypo)thalamic SERT availability were observed in the compulsive dogs. This study provides evidence for imbalanced serotonergic and dopaminergic pathways in the pathophysiology of compulsions in dogs. The similarities with the altered neurotransmission in human OCD provide construct validity for this non-induced, natural canine model, suggesting its usefulness for future investigations of the pathophysiology of human OCD as well as the effectiveness of psychopharmacological interventions.
authors.affiliation: Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Ghent University, Merelbeke, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Vermeire
authors.forename: Kurt
authors.initials: K
authors.lastname: Audenaert
authors.forename: Rudy
authors.initials: R
authors.lastname: De Meester
authors.forename: Eva
authors.initials: E
authors.lastname: Vandermeulen
authors.forename: Tim
authors.initials: T
authors.lastname: Waelbers
authors.forename: Bart
authors.initials: B
authors.lastname: De Spiegeleer
authors.forename: Jos
authors.initials: J
authors.lastname: Eersels
authors.forename: André
authors.initials: A
authors.lastname: Dobbeleir
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003192:Compulsive Behavior / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D044402:Receptor, Serotonin, 5-HT2A; D050486:Serotonin Plasma Membrane Transport Proteins