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 DOI: 10.1096/fasebj.27.1_supplement.1098.10
Summary
AI-generated from the abstractMDMA's behavioral effects are primarily due to central nervous system actions, not peripheral ones. In rats trained to distinguish MDMA from saline, the drug produced dose-related increases in drug-appropriate responses. A quaternary analog of MDMA (qMDMA), which cannot cross the blood-brain barrier, did not substitute for MDMA when given peripherally, but partially substituted when infused directly into the brain. This validates qMDMA as a tool for separating central from peripheral effects of MDMA.
Study at a glance
| Characteristics | Drug discrimination study Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA fenfluramine morphine qMDMA |
| Dose | 1.7 mg/kg MDMA HCl (training dose), 0.56 mg/kg ED50, 300 μg MDMA intraventricular, 250 μg qMDMA intraventricular |
| Key finding | The quaternary MDMA analog (qMDMA) did not substitute for MDMA when given peripherally but partially substituted when infused into the brain, indicating MDMA's behavioral effects are centrally mediated. |
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.