MDMA Self-Administration in Laboratory Animals: A Summary of the Literature and Proposal for Future Research

Use of MDMA has risen globally and shifted from a dance-club subculture to broader, more frequent, high-dose consumption, with some users meeting criteria for abuse or dependence. Because studying human users involves confounding factors, animal models—especially self-administration—are used for their predictive validity. Most studies in primates and rodents show only low daily self-administration of MDMA, though some subjects self-administer high levels, possibly depending on test sessions, prior training, or other variables. MDMA is generally a weaker reinforcer than other drugs of abuse. The review suggests that repeated MDMA exposure reduces serotonin release, and the resulting serotonin deficit enhances dopamine responses, which may drive the development and maintenance of MDMA self-administration.

Study at a glance

Abstract

The prevalence of 3,4-methylenedioxymethamphetamine (MDMA) use has increased globally and the pattern of consumption has changed considerably. Previously, a subculture of MDMA users was fairly restricted to the dance club scene. More recently, use has spread outside of this subculture and now many users consume MDMA frequently and in large amounts and some meet criteria for drug abuse and/or dependence. Because of confounds associated with studying drug users and abusers, animal models have been employed to investigate potential consequences of drug-taking. Among these, self-administration by laboratory animals has been shown to have excellent predictive validity. There have, however, been mixed results with respect to the ability of MDMA to support and maintain self-administration by laboratory animals. This paper reviews the literature on MDMA self-administration in laboratory primates and rodents. Most of the studies in laboratory animals suggest that only low levels of MDMA are self-administered on a daily basis but some have indicated high levels of self-administered MDMA in certain subjects. Differences might be dependent upon the number of test sessions, prior training conditions or other paradigmatic variables. In most cases, MDMA was found to be a lower efficacy reinforcer than other drugs of abuse. It is suggested that the MDMA self-administration develops following a decrease in MDMA-produced serotonin release that occurs with repeated exposure over an extended period of testing. It is hypothesized that the deficit in central serotonin increases the relative MDMA-produced dopamine responses and that this increase in the dopamine response underlies the development and maintenance of MDMA self-administration.