Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A

This study investigated the possible behavioral mechanisms underlying the anorectic effect of the cannabinoid CB1 receptor antagonist/ inverse agonist N-(piperidin-1-yl)- 5 -(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide hydrochloride (SR141716A). Male or female rats were food-restricted and trained to emit stable responding in daily 10-min, fixed ratio 10 food-reinforced operant sessions. Under these conditions, as well as under free-feeding conditions, SR141716A inhibited food-maintained responding (ED50 values ranging from 0.92 to 2.52 mg/kg, i.p.). In the same operant procedure, SR141716A suppressed intracranial self-stimulation with a potency which was slightly lower than the anorectic potency (ED50: 4.50 mg/kg). As assessed during a 10-min test period SR141716A (1-10 mg/kg) did not affect activity counts; suggesting that the observed inhibition of operant behavior is not a direct consequence of impairment of locomotor activity. SR141716A, however, attenuated saccharin-preference in a conditioned taste aversion paradigm (ED50: 6.45 mg/kg). Although the data support the suggestion that the anorectic effect of SR141716A results from an attenuating effect on the rewarding effect of food, the contribution of drug-induced aversion/malaise cannot be excluded. (C) 2003 Elsevier B.V All rights reserved.