, Volume 130, Issue 1, pp 41–58 | Cite as

Serotonergic mechanisms involved in the discriminative stimulus, reinforcing and subjective effects of cocaine

  • Sharon L. Walsh
  • K. A. Cunningham


 The purpose of the present manuscript is to review the current status of the role of serotonin (5-hydroxytryptamine; 5-HT) systems in the stimulus and reinforcing properties of cocaine in non-humans and the subjective effects of cocaine in humans. Review of the current literature suggests that general enhancement (via precursor administration) or depletion of brain 5-HT content (via neurotoxin administration or tryptophan depletion) impact the reinforcing effects of cocaine in non-humans and its subjective effects in humans. Selective 5-HT reuptake inhibitors (SSRIs) enhance the discriminability of cocaine and decrease cocaine self-administration in animals, although data to the contrary also exist. Studies in humans suggest that SSRIs attenuate the subjective effects of cocaine in humans. Although few drugs with selectivity for 5-HT2 receptors have been studied systematically, a 5-HT2 agonist and several antagonists show some efficacy in enhancing and reducing, respectively, the reinforcing effects of cocaine in non-humans. Limited data from humans suggest that a 5-HT2 antagonist may also decrease the subjective effects of cocaine; thus, 5-HT2 compounds deserve further attention. The majority of studies evaluating the 5-HT3 antagonists have reported negative results across all paradigms. In summary, while the functional significance of 5-HT receptors has not been fully elucidated, these data suggest that changes in serotonergic activity can modulate the effects of cocaine in both animals and humans under a variety of experimental conditions. One commonality among the studies with positive findings is that cocaine effects are only partially modified by 5-HT agents regardless of the direction of change.

Key words Cocaine Drug discrimination Dopamine (DA) Human Rat Reuptake inhibitor Reinforcing effects Self-administration Serotonin (5-HT) 5-HT1A 5-HT2 5-HT3 Subjective effects Stimulus effects 


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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Sharon L. Walsh
    • 1
  • K. A. Cunningham
    • 2
  1. 1.Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224-6823, USATP
  2. 2.Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USAUS

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