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

Neuropsychopharmacology. 2001 Aug;25(2):195-203. doi: 10.1016/S0893-133X(01)00222-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology*
  • Animals
  • Biogenic Amines / biosynthesis*
  • Brain / drug effects*
  • Brain / metabolism
  • Cocaine / pharmacology*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Injections, Intravenous
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration


  • Adrenergic Uptake Inhibitors
  • Biogenic Amines
  • Dopamine Uptake Inhibitors
  • Cocaine
  • N-Methyl-3,4-methylenedioxyamphetamine