Discriminative‐stimulus effects of 3,4‐methylenedioxy‐N‐methylamphetamine (MDMA) and a novel MDMA quatenary analog
Jonathan M. Slezak, Melanie Mueller, George A Ricaurte, Jianjing Cao, Amy H. Newman, Jonathan L. Katz
The FASEB Journal April 1, 2013 Peer reviewed DOI: 10.1096/fasebj.27.1_supplement.1098.10
Summary
MDMA increased the percentage of responses on the drug-appropriate key in male Sprague-Dawley rats, with an effective dose (ED50) of 0.56 mg/kg. The study showed that neither morphine nor a quaternary analog of MDMA (qMDMA) substituted for MDMA, while fenfluramine and oral MDMA did. Additionally, intraventricular administration of MDMA led to full substitution at 300 μg, and partial substitution with qMDMA at 250 μg, indicating the potential for studying MDMA's central versus peripheral effects.
Study at a glance
| Design | experimental study |
|---|---|
| Sample size | 6 |
| Population | male Sprague-Dawley rats |
| Key finding | MDMA produced dose-related increases in drug-appropriate responses with an ED50 value of 0.56 mg/kg. |
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.