Molecular Neurobiology

, Volume 11, Issue 1, pp 1–19

A review of the effects of dopaminergic agents on humans, animals, and drug-seeking behavior, and its implications for medication development

Focus on GBR 12909
  • Richard B. Rothman
  • John R. Glowa
Proceedings of the Symposium Cellular and Molecular Mechanisms of Drugs of Abuse Cocaine and Methamphetamine held in Nice, France, August 19–20, 1993

DOI: 10.1007/BF02740680

Cite this article as:
Rothman, R.B. & Glowa, J.R. Mol Neurobiol (1995) 11: 1. doi:10.1007/BF02740680


Medication development for cocaine abuse has focused on potential mechanisms of action related to the abuse of cocaine. The hypothesis that mesolimbic dopamine (DA) is the key neurochemical mediator of cocaine’s addictive and reinforcing effects is well supported by a wide variety of data from animal studies. On the other hand, medications that increase DA or block its actions in humans can produce effects that appear incompatible with this hypothesis. This article reviews these incompatibilities between animal and human data with a focus on the DAergic actions of drugs, including DA reuptake inhibitors, direct DA agonists, DA increasers, and DA antagonists. Possible reasons for these discrepancies are discussed, and the potential role of high-affinity DA uptake inhibitors, such as GBR12909, for pharmacotherapeutic application to treat cocaine abuse is discussed. Since progress in developing pharmacotherapies for treating cocaine addiction in humans is likely to come from understanding its mechanisms of action, it is clear that further research on the effects of cocaine in humans and animals will be critical to the medication development effort.

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Copyright information

© Human Press Inc 1995

Authors and Affiliations

  • Richard B. Rothman
    • 1
  • John R. Glowa
    • 2
  1. 1.Clinicla Psychopharmacology Section, IRP, NIDANIHBaltimore
  2. 2.Behavioral Pharmacology UnitLMC/NIDDK/NIHBethesda