Pre-exposure to (+/-)3,4-methylenedioxy-methamphetamine (MDMA) facilitates acquisition of intravenous cocaine self-administration in rats.
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.
Fletcher
P J
PJ
Section of Biopsychology, Department of Psychiatry, University of Toronto, Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada. fletcher@psych.toronto.edu
Robinson
S R
SR
Slippoy
D L
DL
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000096:biosynthesis*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D018759:Adrenergic Uptake Inhibitors; D001679:Biogenic Amines; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine