Role of Cannabinoid CB1 Receptor in Morphine Rewarding Effects in Mice

Abstract

It has been reported that, as well as morphine, the cannabinoid CB1 receptor agonist WIN 55,212-2 failed to induce intravenous self- administration in mutant CB1 receptor knockout (CB1(-/-)) mice but not in the corresponding wild type (CB1(+/+)) mice. To verify whether this functional interaction responsible for opioid rewarding effects was specific or could also be extended to other drugs of abuse, we have evaluated the ability of cocaine, amphetamine and nicotine to induce intravenous self- administration in both CB1(-/-) and CB1(+/+) mice. The results showed that, contrary to morphine, the other drugs of abuse were intravenously self- administered to the same extent by both wild type and CB1(-/-) mice. This points to a specific role of the CB1 receptor in the opioid motivational and rewarding properties. In addition, since mesolimbic dopamine transmission is known to have a pivotal role in reward mediation, the effect of morphine on limbic dopamine release in CB1(-/-) and CB1(+/+) mice has been investigated and compared with the effect of cocaine. Morphine did not modify dopamine release in the nucleus accumbens of CB1(-/-) mice whereas it dose- dependently stimulated dopamine release in the corresponding CB1(+/+) mice. In contrast, cocaine increased dopamine release in both strains of mice, showing that its effect on dopamine transmission was not linked to the cannabinoid system. Taken together, our results clearly show that the CB1 receptor is essential for the expression of the behavioural and biochemical effects of morphine. This extends previous observations on a functional specific interaction between endogenous cannabinoid and opiate systems in the central mechanisms of reward.