Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents

Abstract

The endocannabinoid system has been implicated in the modulation of emotional processes. These experiments aimed to investigate the effects of the cannabinoid CB1 receptor antagonist rimonabant (SR141716) in animal models measuring aspects of emotional reactivity and depression. Rimonabant had weak anxiolytic-like activity in the elevated plus-maze and failed to affect flight and risk assessment activities in the mouse defense test battery (MDTB). It produced clear anxiolytic-like effects in the Vogel conflict test (.3-3 mg/kg intraperitoneal [i.p.]) and on defensive aggression in the MDTB (1 and 10 mg/kg, i.p.). The effects of rimonabant in the MDTB paralleled those observed with CB1 receptor knockout mice in this procedure. In the forced-swimming test in rats and the tonic immobility paradigm in gerbils, rimonabant (3 and 10 mg/kg per os [p.o.]) produced antidepressant-like effects that were comparable to those observed with the reference antidepressant, fluoxetine. In the chronic mild stress model in mice, repeated administration of rimonabant (10 mg/kg, p.o.) for 5 weeks improved the deleterious effects produced by stress. These findings point further to a role for the endocannabinoid system in the modulation of emotional processes and suggest that it may be primarily involved in the adaptive responses to unavoidable stressful stimuli.