title: Effects of various cannabinoid ligands on choice behaviour in a rat model of gambling.
abstract: It is estimated that 0.6-1% of the population in the USA and Canada fulfil the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5) criteria for gambling disorders (GD). To date, there are no approved pharmacological treatments for GD. The rat gambling task (rGT) is a recently developed rodent analogue of the Iowa gambling task in which rats are trained to associate four response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. Similar to healthy human volunteers, most rats adopt the optimal strategies (optimal group). However, a subset of animals show preference for the disadvantageous options (suboptimal group), mimicking the choice pattern of patients with GD. Here, we explored for the first time the effects of various cannabinoid ligands (WIN 55,212-2, AM 4113, AM 630 and URB 597) on the rGT. Administration of the cannabinoid agonist CB1/CB2 WIN 55,212-2 improved choice strategy and increased choice latency in the suboptimal group, but only increased perseverative behaviour, when punished, in the optimal group. Blockade of CB1 or CB2 receptors or inhibition of fatty-acid amide hydrolase did not affect rGT performance. These results suggest that stimulation of cannabinoid receptors could affect gambling choice behaviours differentially in some subgroups of subjects.
authors.affiliation: aTranslational Addiction Research Laboratory bAlcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments cCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health Departments of dFamily and Community Medicine ePharmacology fDepartment of Psychiatry, Division of Brain and Therapeutics gInstitute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada hDepartment of Pharmaceutical Sciences and Chemistry and Chemical Biology, Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA.
authors.forename: Aliou B
authors.initials: AB
authors.lastname: Gueye
authors.forename: Jose M
authors.initials: JM
authors.lastname: Trigo
authors.forename: Kiran V
authors.initials: KV
authors.lastname: Vemuri
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000627:therapeutic use*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D005715:Gambling / Q000188:drug therapy*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D012054:Reinforcement, Psychology
chemical_list: D063385:Cannabinoid Receptor Modulators