Assessment of the abuse potential of MDMA in the conditioned place preference paradigm: role of CB1 receptors.

Numerous reports have highlighted the role of the endocannabinoid system in the addictive potential of MDMA (3,4-methylenedioxy-methamphetamine). A previous report showed that CB1 knockout (KOCB1) mice do not acquire MDMA self-administration, despite developing conditioned place preference (CPP). This contradiction could be due to the particular procedure of place conditioning used. The present work compares MDMA-induced CPP in KOCB1 mice using unbiased and biased procedures of place conditioning. In the unbiased procedure, MDMA induced CPP and reinstatement of the extinguished preference in wild type (WT) mice, but not in KOCB1 mice. In contrast, in a biased protocol of CPP, MDMA produced preference in both types of mice. The anxiolytic response induced by MDMA in the elevated plus maze (EPM) was observed only in KOCB1 mice and may have been responsible, at least partially, for the CPP in the biased procedure. A neurochemical analysis revealed that KOCB1 mice presented higher striatal DA and DOPAC levels in response to MDMA, but no alterations in their levels of monoamine transporters. In line with previous self-administration studies, our data suggest that CB1 receptors play an important role in the reinforcing effects of MDMA, and that the experimental procedure of CPP employed should be taken into account when drawing conclusions.