Cannabinoid CB1 receptor knockout mice fail to self-administer morphine but not other drugs of abuse

The rewarding effects of morphine, cocaine, amphetamine and nicotine were e valuated in CB1 receptor knockout mice by means of an intravenous self-admi nistration model. Experiments were carried out on drug-naive animals using a nose-poking response (NPR)-like as operandum. The results of the present study indicate that morphine did not induce intravenous self-administration in mutant CB1 receptor knockout mice, whereas it was significantly self-ad ministered by the corresponding wild type mice. On the contrary, cocaine, a mphetamine and nicotine were self-administered to the same extent by both w ild type and CB1 receptor knockout mice. These data clearly indicate that t he CB1 cannabinoid receptor is essential not only for the expression of can nabinoid reinforcing effects but also for the modulation of morphine reward ing effects. The specificity of such interaction is supported by the findin g that contrary to morphine, cocaine, d-amphetamine and nicotine were self- administered by mice at the same extent either in presence or in absence of the CB1 receptor. (C) 2001 Elsevier Science B.V. All rights reserved.