Skip to content

MDMA self‐administration in rats: acquisition, progressive ratio responding and serotonin transporter binding

Susan Schenk, Lincoln S. Hely, Barbara Lake, Evangelene Joy Kia Daniela, David Gittings, Deborah C. Mash

European Journal of Neuroscience November 16, 2007 DOI: 10.1111/j.1460-9568.2007.05932.x (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions MDMA cocaine
Dose 0.25 or 1.0 mg/kg/infusion
Duration 15-day test period, daily 6-h sessions
Topics MDMA Serotonin
Keywords Self-administration Pharmacology Citalopram Serotonin transporter Anesthesia
Citations 113
Key findings MDMA self-administration led to lower serotonin transporter densities across brain regions, comparable to experimenter-administered MDMA, supporting high abuse liability and lasting serotonin deficits.

Abstract

Abstract 3,4‐Methylenedioxymethamphetamine (MDMA) self‐administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug‐naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self‐administration was measured during daily 6‐h sessions. Dose–effect data were obtained for MDMA (0.25–1.0 mg/kg/infusion) self‐administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter‐ or self‐administered MDMA on [ 3 H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self‐administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self‐administration during the 15‐day test period. The percentage of rats that acquired MDMA self‐administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self‐administration, and cocaine self‐administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self‐administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter‐administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long‐term self‐administration may lead to long‐lasting deficits in serotonin neurotransmission.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

Citations in the library

Cited by 44

and 39 more in the library

Cites 17

and 12 more in the library

Related reading

Explore topics

MDMA Serotonin Addiction