CB1 cannabinoid receptor agonist WIN 55,212-2 decreases intravenous cocaine self-administration in rats

The effect of the CB, cannabinoid receptor agonist WIN 55, 212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55, 212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB, receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55, 212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB, cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine. (C) 1999 Elsevier Science B.V. All rights reserved.