Pre-exposure to (+/-)3,4-methylenedioxy-methamphetamine (MDMA) facilitates acquisition of intravenous cocaine self-administration in rats
Fletcher PJ, Robinson SR, Slippoy DL.
Section of Biopsychology, Department of Psychiatry,
University of Toronto,
Centre for Addiction and Mental Health, Clarke Division,
Toronto, Ontario, Canada.
Neuropsychopharmacology 2001 Aug;25(2):195-203


Pre-exposure to (+/-)3,4-methylenedioxymeth-amphetamine (MDMA) elevates locomotor activity and extracellular dopamine levels in the nucleus accumbens following a cocaine challenge. The present study determined whether MDMA-induced sensitization to the effects of cocaine could be demonstrated in rats 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 (twice 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 lever delivered infusions of 0.1 mg of cocaine; responses on the other lever had no programmed consequences. Group Sal showed a weak preference for the active lever; whereas, group MDMA-20 exhibited a stronger active lever preference. By day 12, the MDMA-20 group earned approximately twice the number of cocaine infusions as those in group SAL. At this time point, more than twice 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 differ from group Sal in terms of lever discrimination, number of cocaine infusions, and percentage of rats obtaining a criterion of 10 infusions. These results indicate that pre-exposure to a high dose of MDMA may facilitate acquisition of cocaine self-administration. This dosing regimen of MDMA is likely 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 cocaine self-administration.

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