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

Background: The endocannabinoid system has been implicated in the modulation of emotional processes. Methods: 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. Results: Rimonabant bad 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. Conclusions: 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.