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

Academic Article
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Overview

authors

  • Rocha, B. A.
  • Goulding, E. H.
  • O'Dell, L. E.
  • Mead, A. N.
  • Coufal, N. G.
  • Parsons, Loren (Larry)
  • Tecott, L. H.

publication date

  • November 2002

journal

  • Journal of Neuroscience  Journal

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.

subject areas

  • Animals
  • Behavior, Animal
  • Brain Chemistry
  • Cocaine
  • Cocaine-Related Disorders
  • Conditioning, Operant
  • Corpus Striatum
  • Disease Models, Animal
  • Dopamine
  • Drug Resistance
  • Exploratory Behavior
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microdialysis
  • Motor Activity
  • Nucleus Accumbens
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Reinforcement (Psychology)
  • Self Administration
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Research

keywords

  • behavior
  • cocaine
  • mice
  • reinforcement
  • serotonin
  • serotonin 2c receptor
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

PubMed ID

  • 12427861
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Additional Document Info

start page

  • 10039

end page

  • 10045

volume

  • 22

issue

  • 22

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