Psychopharmacology

, Volume 210, Issue 1, pp 75–83

Reinstatement of extinguished amphetamine self-administration by 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys

  • Jessica McClung
  • William Fantegrossi
  • Leonard L. Howell
Original Investigation

DOI: 10.1007/s00213-010-1818-7

Cite this article as:
McClung, J., Fantegrossi, W. & Howell, L.L. Psychopharmacology (2010) 210: 75. doi:10.1007/s00213-010-1818-7

Abstract

Rationale

The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated.

Objectives

The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/–)-MDMA, S(+)-MDMA, R(–)-MDMA, and  fenfluramine on behavior maintained under a second-order schedule of intravenous amphetamine self-administration in rhesus monkeys (n=4).

Methods

Following saline substitution and extinction, a range of doses of amphetamine, BZP, SR(+/–)-MDMA, S(+)-MDMA, R(–)-MDMA, and fenfluramine were administered i.v. as non-contingent priming injections in order to characterize their effectiveness to reinstate responding previously maintained by amphetamine self-administration.

Results

Priming injections of amphetamine, BZP, SR(+/–)-MDMA, and S(+)-MDMA induced significant reinstatement effects. In contrast, neither R(–)-MDMA nor fenfluramine effectively reinstated behavior. Pretreatment with the selective serotonin transporter inhibitor, fluoxetine, attenuated the reinstatement effects of SR(+/–)-MDMA, S(+)-MDMA, and BZP but had no significant effect on amphetamine-primed reinstatement.

Conclusions

Given the profile of neurochemical effects published previously, these findings suggest that the reinstatement effects of MDMA are mediated primarily by dopamine release; however, the attenuation of MDMA-induced reinstatement by fluoxetine supports previous research demonstrating the complex behavioral pharmacology of MDMA-like drugs and that the reinstatement effects of MDMA are at least partially mediated by serotonergic mechanisms.

Keywords

AmphetamineMDMABZPReinstatementRhesus monkey

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jessica McClung
    • 1
  • William Fantegrossi
    • 2
    • 3
  • Leonard L. Howell
    • 1
    • 4
  1. 1.Division of Neuroscience, Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  2. 2.Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  3. 3.Department of Pharmacology and ToxicologyUniversity of Arkansas for Medical SciencesLittle RockUSA
  4. 4.Department of Psychiatry and Behavioral SciencesEmory UniversityAtlantaUSA