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

Sharon L. Walsh, Kathryn A. Cunningham

Research output: Contribution to journalReview articlepeer-review

195 Scopus citations


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.

Original languageEnglish
Pages (from-to)41-58
Number of pages18
Issue number1
StatePublished - 1997

Bibliographical note

Funding Information:
&p.2: wledgements Preparation of this manuscript was supported by National Institute on Drug Abuse grants DA 10029 (S.L.W.), and DA 06511 and DA 00260 (K.A.C.). The authors wish to thank Dr. Steven I. Dworkin for his helpful comments.


  • 5-HT
  • 5-HT
  • 5-HT(1A)
  • Cocaine
  • Dopamine (DA)
  • Drug discrimination
  • Human
  • Rat
  • Reinforcing effects
  • Reuptake inhibitor
  • Self-administration
  • Serotonin (5-HT)
  • Stimulus effects
  • Subjective effects

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'Serotonergic mechanisms involved in the discriminative stimulus, reinforcing and subjective effects of cocaine'. Together they form a unique fingerprint.

Cite this