Serotonin (5-hydroxytryptamine) 5-HT2A receptor: Association with inherent and cocaine-evoked behavioral disinhibition in rats

Noelle C. Anastasio, Erin C. Stoffel, Robert G. Fox, Marcy J. Bubar, Kenner C. Rice, Frederick G. Moeller, Kathryn A. Cunningham

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT 2AR as an important regulatory substrate in impulse control.

Original languageEnglish (US)
Pages (from-to)248-261
Number of pages14
JournalBehavioural Pharmacology
Volume22
Issue number3
DOIs
StatePublished - Jun 2011

Keywords

  • 5-HT receptor
  • behavioral disinhibition
  • cocaine
  • differential reinforcement of low rate task
  • impulsivity
  • one-choice serial reaction time task
  • rat

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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