MDMA self-administration in rats: Acquisition, progressive ratio responding and serotonin transporter binding

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

Research output: Contribution to journalArticle

52 Scopus citations

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 [ 3H] 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.

Original languageEnglish (US)
Pages (from-to)3229-3236
Number of pages8
JournalEuropean Journal of Neuroscience
Volume26
Issue number11
DOIs
StatePublished - Dec 1 2007

Keywords

  • Drug reinforcement
  • MDMA abuse
  • Neuroadaptation

ASJC Scopus subject areas

  • Neuroscience(all)

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