SELF-ADMINISTRATION OF THE CANNABINOID RECEPTOR AGONIST WIN-55,212-2 IN DRUG-NAIVE MICE

Marijuana is one of the most widely used illicit recreational drugs, H owever, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intr avenous self-administration model in drug-naive mice. The results of t his study show that WIN 55,212-2 was intravenously self-administered b y mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increas ed, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55, 212-2 concentration of 0.5 mg/kg per injection, self-administration si gnificantly decreased, The results obtained show how WIN 55,212-2 is a ble to elicit both rewarding and aversive effects depending on the con centration used. Pretreatment of mice with the cannabinoid CB1 recepto r antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55 ,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoi d CB1 receptors, (C) 1998 LBRO, Published by Elsevier Science Ltd.