Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2011-03, Vol.35 (2), p.434-438
• Main Authors: Gomes, Felipe V., Casarotto, Plinio C., Resstel, Leonardo B.M., Guimarães, Francisco S.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; AM404; Amidohydrolases - antagonists & inhibitors; Animals; Anxiety disorders. Neuroses; Arachidonic Acids - metabolism; Arachidonic Acids - pharmacology; Behavior, Animal - drug effects; Benzamides - pharmacology; Benzoxazines - pharmacology; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cannabinoids; Cannabinoids - pharmacology; Carbamates - pharmacology; Drug Interactions; Endocannabinoids; Male; Marble burying test; Medical sciences; Mice; Mice, Inbred C57BL; Morpholines - pharmacology; Motor Activity - drug effects; Naphthalenes - pharmacology; Neuropharmacology; Obsessive-Compulsive Disorder - drug therapy; Obsessive-Compulsive Disorder - physiopathology; Obsessive-compulsive disorders; Obsessive–compulsive disorder; Pharmacology. Drug treatments; Piperidines - pharmacology; Polyunsaturated Alkamides - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Pyrazoles - pharmacology; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; Synaptic Transmission - drug effects; URB597; WIN55,212-2
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2010.11.027

Obsessive–compulsive disorder (OCD) is a common psychiatric disorder characterized by the occurrence of obsessions and compulsions. Glutamatergic abnormalities have been related to the pathophysiology of OCD. Cannabinoids inhibit glutamate release in the central nervous system, but the involvement of drugs targeting the endocannabinoid system has not yet been tested in animal models of repetitive behavior. Thus, the aim of the present study was to verify the effects of the CB1 receptor agonist WIN55,212-2, the inhibitor of anandamide uptake AM404 and the anandamide hydrolysis inhibitor URB597, on compulsive-associate behavior in male C57BL/6J mice submitted to the marble burying test (MBT), an animal model used for anti-compulsive drug screening. WIN55,212-2 (1 and 3mg/kg), AM404 (1 and 3mg/kg) and URB597 (0.1, 0.3 and 1mg/kg) induced a significant decrease in the number of buried marbles compared to controls. Pretreatment with the CB1 receptor antagonist, AM251, prevented both WIN55,212-2 and URB597 effects. These results suggest a potential role for drugs acting on the cannabinoid system in modulating compulsive behavior. ► Activation of CB1 receptors reduces repetitive behavior in mice. ► CB1 acting drugs reduce the number of buried marbles in the marble burying test. ► CB1 receptors could regulate mice burying behavior.