Abstract
MDMA (ecstasy), popularized as a “club drug,” is a psychoactive and abused substance. It is often assumed that the behavioral effects of MDMA are due to central actions, though this has not been tested. Using a quaternary analog of MDMA (qMDMA) we tested that assumption by training male Sprague‐Dawley rats (n = 6) to discriminate intraperitoneal (i.p.) injections of 1.7 mg/kg of MDMA HCl from saline in a two‐lever discrimination procedure. When MDMA was administered before daily sessions, responses on one of two keys intermittently produced food presentation; responses on the alternate key produced occasional food deliveries after saline injections. MDMA produced dose‐related increases in the percentage of responses on the drug‐appropriate key with an ED50 value of 0.56 mg/kg. In addition the serotonin releaser fenfluramine (i.p.), as well as p.o. MDMA produced dose‐dependent substitution for MDMA. Neither morphine (i.p.) nor qMDMA (i.p.) substituted for MDMA across a range of doses from those having no effect to those decreasing response rates. When MDMA and qMDMA were administered via intraventricular cannulae, full substitution was obtained at 300 μg of MDMA immediately after infusion and partial substitution (~75%) was obtained with the quaternary compound at 250 μg when subjects were tested one hr after infusion. These results validate qMDMA as a tool for investigating central vs. peripheral actions of MDMA.
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