Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytryptamine 2C receptor mutant mice

Beatriz A. Rocha, Evan H. Goulding, Laura E. O'Dell, Andy N. Mead, Nicole G. Coufal, Loren H. Parsons, Laurence H. Tecott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

Abstract

Brain serotonin [5-hydroxytryptamine (5-HT)] systems substantially influence the effects of cocaine; however, the contributions of individual 5-HT receptor subtypes to the regulation of cocaine responses are unclear. A line of mutant mice devoid of 5-HT2C receptors was used to examine the contribution of this receptor subtype to the serotonergic modulation of cocaine responses. Mutants display enhanced exploration of a novel environment and increased sensitivity to the locomotor stimulant effects of cocaine. In an operant intravenous self-administration model under a progressive ratio schedule of reinforcement, mutants display elevated levels of lever pressing for cocaine injections, indicating that the drug is more reinforcing in these mice. Moreover, mutants exhibit enhanced cocaine-induced elevations of dopamine (DA) levels in the nucleus accumbens, a brain region implicated in the stimulant and rewarding properties of cocaine. In contrast, phenotypic differences in dorsal striatal DA levels were not produced by cocaine treatment. These findings strongly implicate 5-HT2C receptors in the serotonergic suppression of DA-mediated behavioral responses to cocaine and as a potential therapeutic target for cocaine abuse.

Original languageEnglish (US)
Pages (from-to)10039-10045
Number of pages7
JournalJournal of Neuroscience
Volume22
Issue number22
DOIs
StatePublished - Nov 15 2002

Keywords

  • Behavior
  • Cocaine
  • Mice
  • Reinforcement
  • Serotonin
  • Serotonin 2c receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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