Development, maintenance and temporal pattern of self-administration maintained by ecstasy (MDMA) in rats

Rationale. +/-3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) use is increasing around the globe but there is a paucity of studies examining the abuse liability of this drug. Objectives. The ability of drugs to reinforce operant responding in laboratory animals is a valid and reliable predictor of abuse potential. MDMA is self-administered by humans, but there have been few reports of reliable self-administration by drug-naive laboratory animals. The present study sought to examine the acquisition and maintenance of MDMA self-administration by laboratory rats. The influence of prior training with cocaine self-administration on the acquisition of MDMA self-administration was also examined. Methods. MDMA self-administration (0.25-2.0 mg/kg per infusion) was examined in rats that were first trained to self-administer cocaine as well as by those that were drug-naive. The dose-dependency of MDMA self-administration and the temporal pattern of responding maintained by various doses of MDMA were examined. In some rats, self-administration of MDMA during a 24-h session was also examined. Results. MDMA was self-administered by laboratory rats that were experienced with self-administration of cocaine as well as by rats that were initially drug naive. For drug naive rats, the acquisition of MDMA self-administration (1.0 mg/kg per infusion) developed gradually during daily test sessions. The latency to acquisition of self-administration was shorter in cocaine-trained rats. Self-administration was dose-dependent, extinguished when saline was substituted for MDMA and, was reinstated when MDMA was reintroduced. During a 24-h self-administration session, a high rate of responding was produced during the first hour of the test session followed by a steady and lower rate of two to four responses per hour during subsequent hours of the test. Conclusions. These results suggest that prior experience with cocaine self-administration facilitates the acquisition of MDMA self-administration. The results also suggest that MDMA has abuse liability and that increased use of the drug should raise concern of a growing and widespread potential for chronic abuse.