Background: 3, 4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug widely abused by young people. The endocannabinoid system is involved in the addictive processes induced by different drugs of abuse. However, the role of this system in the pharmacological effects of MDMA has not been yet clarified./nMethods: Locomotion, body temperature and anxiogenic-like responses were evaluated after acute MDMA administration in CB1 knockout mice. Additionally, MDMA rewarding properties were investigated in the place conditioning and the intravenous self-administration paradigms. Extracellular levels of DA in the nucleus accumbens were also analyzed after a single administration of MDMA by in vivo microdialysis. Results: Acute MDMA administration increased locomotor activity, body temperature and anxiogenic-like responses in wild type mice, but these responses were lower or abolished in knockout animals. MDMA produced similar conditioned place preference and increased dopamine extracellular levels in the nucleus accumbens in both genotypes. Nevertheless, CB1 knockout mice failed to self-administer MDMA at any of the doses used. Conclusions: These results indicate that CB1 cannabinoid receptors play an important role in the acute prototypical effects of MDMA, and are essential in the acquisition of an operant behavior to self-administer this drug.

This study was supported by grants from Spanish MCYT (SAF 2004/568 to OV; BFU2004-00920/BFI and GEN2003-20651-C06-04 to RM), and MSC (Plan Nacional sobre Drogodependencias, conv-2006) to OV, Generalitat de Catalunya (2005SGR00141), European Communities (GENADDICT LSHM–CT–2004–005166) to RM. CT has a fellowship supported by the Department of Education and Universities from Generalitat de Catalunya and by the Social European Fund.