Serotonin 5-HT2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder

Leonard L. Howell, Kathryn Cunningham

Research output: Contribution to journalReview article

85 Citations (Scopus)

Abstract

Cocaine exhibits prominent abuse liability, and chronic abuse can result in cocaine use disorder with significant morbidity. Major advances have been made in delineating neurobiological mechanisms of cocaine abuse; however, effective medications to treat cocaine use disorder remain to be discovered. The present review will focus on the role of serotonin (5-HT; 5-hydroxytryptamine) neurotransmission in the neuropharmacology of cocaine and related abused stimulants. Extensive research suggests that the primary contribution of 5-HT to cocaine addiction is a consequence of interactions with dopamine (DA) neurotransmission. The literature on the neurobiological and behavioral effects of cocaine is well developed, so the focus of the review will be on cocaine with inferences made about other monoamine uptake inhibitors and releasers based on mechanistic considerations. 5-HT receptors are widely expressed throughout the brain, and several different 5-HT receptor subtypes have been implicated in mediating the effects of endogenous 5-HT on DA. However, the 5-HT2A and 5-HT2C receptors in particular have been implicated as likely candidates for mediating the influence of 5-HT in cocaine abuse as well as to traits (e.g., impulsivity) that contribute to the development of cocaine use disorder and relapse in humans. Lastly, new approaches are proposed to guide targeted development of serotonergic ligands for the treatment of cocaine use disorder.

Original languageEnglish (US)
Pages (from-to)176-197
Number of pages22
JournalPharmacological Reviews
Volume67
Issue number1
DOIs
StatePublished - 2015

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Serotonin 5-HT2 Receptors
Cocaine
Dopamine
Serotonin
Cocaine-Related Disorders
Serotonin Receptors
Therapeutics
Synaptic Transmission
Neuropharmacology
Receptor, Serotonin, 5-HT2C
Impulsive Behavior
Ligands
Morbidity
Recurrence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Serotonin 5-HT2 receptor interactions with dopamine function : implications for therapeutics in cocaine use disorder. / Howell, Leonard L.; Cunningham, Kathryn.

In: Pharmacological Reviews, Vol. 67, No. 1, 2015, p. 176-197.

Research output: Contribution to journalReview article

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