Pre-exposure to (+/-)3,4-methylenedioxy-methamphetamine (MDMA) facilitatesacquisition of intravenous cocaine self-administration in rats

Pre-exposure to (+/- )3,4-methylenedioxymeth-amphetamine (MDMA) elevates lo comotor activity and extracellular dopamine levels in the nucleus accumbens following a cocaine challenge. The present study determined whether MDMA-i nduced sensitization to the effects of cocaine could be demonstrated in rat s self-administering cocaine. Three groups of rats were treated with saline (Sal), 5 mg/kg MDMA (once per day for 10 days; MDMA-5) or 20 mg/kg MDMA (t wice per day for 4 days; MDMA-20). Subsequently, spontaneous acquisition of cocaine self-administration was measured in 12 daily 2-h sessions. During these test sessions, two response levers were present. Responses on one lev er delivered infusions of 0.1 mg of cocaine; responses on the other lever h ad no programmed consequences. Group Sal showed a weak preference for the a ctive lever; whereas, group MDMA-20 exhibited a stronger active lever prefe rence. By day 12, the MDMA-20 group earned approximately twice the number o f cocaine infusions as those in group SAL. At this time point, more than tw ice as many rats in group MDMA-20 were taking a minimum of 10 infusions per session, as compared to group Sal. Rats in group MDMA-5 did not seem to di ffer from group Sal in terms of lever discrimination, number of cocaine inf usions, and percentage of rats obtaining a criterion of 10 infusions. These results indicate that pre-exposure to a high dose of MDMA may facilitate a cquisition of cocaine self-administration. This dosing regimen of MDMA is l ikely to release DA and to be neurotoxic to 5-HT neurons. Either or both of these mechanisms could contribute to the ability of MDMA to facilitate coc aine self-administration. [Neuropsychopharmacology 25:195-203, 2001] (C) 20 01 American College of Neuropsychopharmacology. Published by Elsevier Scien ce Inc.