Cannabinoid CB1 receptor antagonism markedly increases dopamine receptor-mediated stereotypies

The contribution of the endocannabinoid system to dopamine-mediated disorganized behavior in schizophrenia is discussed. We used a model of concurrent stimulation of dopamine D-1 and D-2 receptors to evaluate the role of this system in dopamine-mediated stereotypies measured in a hole-board test. Pretreatment with the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A; I mg/kg) potentiated stereotyped behavior induced by coadministration of the dopamine D-1 receptor agonist SKF 38393 (0.05, 0.1 and I mg/kg) and the dopamine D-2 receptor agonist quinpirole (0.25 mg/kg). Thus, the endocannabinoid system acts as a brake for abnormal behavior associated with dopaminergic overactivation. (c) 2007 Elsevier B.V. All rights reserved.