Psychopharmacology

, Volume 141, Issue 3, pp 287–296

Effects of dopamine and serotonin-releasing agents on methamphetamine discrimination and self-administration in rats

  • Patrik Munzar
  • Michael H. Baumann
  • Mohammed Shoaib
  • S. R. Goldberg
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130050836

Cite this article as:
Munzar, P., Baumann, M., Shoaib, M. et al. Psychopharmacology (1999) 141: 287. doi:10.1007/s002130050836

Abstract

 To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.

Key words Methamphetamine Dopamine Serotonin Phentermine Fenfluramine Drug-discrimination Self-administration Rat 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Patrik Munzar
    • 1
  • Michael H. Baumann
    • 2
  • Mohammed Shoaib
    • 1
  • S. R. Goldberg
    • 1
  1. 1.Preclinical Pharmacology Laboratory, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA Fax: +1-410-550-1648, e-mail:sgoldber@intra.nida.nih.govTP
  2. 2.Clinical Psychopharmacology Section, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USATP
  3. 3.Department of Pharmacology, Faculty of Medicine, Masaryk University, Joˇstova 10, 66243 Brno, Czech RepublicXX
  4. 4.Section of Behavioural Pharmacology, Institute of Psychiatry, DeCrespigny Park, London SE5 8AF, UKGB

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