CB1 cannabinoid receptor modulates 3,4-methylenedioxymethamphetamine acute responses and reinforcement

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug widely abused by young people. The endo-cannabinoid 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 yet been clarified. Methods: Locomotion, body temperature, and anxiogenic-like responses were evaluated after acute MDMA administration in CB, cannabinoid receptor I knockout mice. Additionally, MDMA rewarding properties were investigated in the place conditioning and the intravenous self-administration paradigms. Extracellular levels of dopamine (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. 3,4-Methylenedioxymethamphetamine produced similar conditioned place preference and increased dopamine extracellular levels in the nucleus accumbens in both genotypes. Nevertheless, CB, knockout mice failed to self-administer MDMA at any of the doses used. Conclusions: These results indicate that CB, 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.