Effects of rimonabant on the development of single dose-induced behavioral sensitization to ethanol, morphine and cocaine in mice

Rationale: The endocannabinoid system has been implicated in the neurobiological mechanism underlying drug addiction, especially the primary rewarding dopamine-dependent processes. Therefore, endocannabinoid receptor antagonists, such as the CB1 cannabinoid antagonist rimonabant, have been proposed as candidates for preventive addiction therapies. Objectives: Investigate the possible involvement of CB1 receptors in the development of behavioral sensitization to ethanol, morphine and cocaine in mice. Methods: We compared the effects of different doses of rimonabant (0.3, 1, 3 and 10 mg/kg) on spontaneous locomotor activity in the open-field, hyperlocomotion induced by acute administration of ethanol (1.8 g/kg), morphine (20 mg/kg) or cocaine (10 mg/kg) and on subsequent drug-induced locomotor sensitization using a two-injection protocol in mice. We also investigated a possible depressive-like effect of an acute rimonabant challenge at the highest dose and its potential anxiogenic property. Results: At the highest dose, rimonabant abolished ethanol-and cocaine-induced hyperlocomotion and behavioral sensitization without modifying spontaneous and central locomotor activity or inducing depressive-like behavior on the forced swim test in mice. The other doses of rimonabant also selectively blocked acute ethanol-induced central hyperlocomotion. Although rimonabant at 0.3 and 1 mg/kg potentiated the central hyperlocomotion induced by acute morphine injection, it was effective inattenuating morphine-induced behavioral sensitization at all doses. Conclusions: Because the neural basis of behavioral sensitization has been proposed to correspond to some components of addiction, our findings indicate that the endocannabinoid system might be involved in ethanol, cocaine and morphine abuse. (C) 2014 Elsevier Inc. All rights reserved.