Opposing Roles for 5-HT2A and 5-HT2C Receptors in the Nucleus Accumbens on Inhibitory Response Control in the 5-choice Serial Reaction Time Task

Neuropsychopharmacology. 2008 Sep;33(10):2398-406. doi: 10.1038/sj.npp.1301636. Epub 2007 Nov 28.

Abstract

Serotonin (5-HT) is thought to play an important role in the regulation of behavioral inhibition. Studies manipulating 5-HT function in the rodent brain indicate that 5-HT receptors regulate distinct forms of impulsive behavior, including impulsive responding in the 5-choice serial reaction time task (5CSRTT). The present study investigates the loci of effects mediated by 5-HT(2A) and 5-HT(2C) receptors in attention and inhibitory response control using microinfusions targeted at the nucleus accumbens (NAc), prelimbic cortex (PL) and infralimbic cortex (IL). Rats were implanted with bilateral guide cannulas and received infusions of the selective 5-HT(2A) receptor antagonist M100907 (0.1 and 0.3 microg) or selective 5-HT(2C) receptor antagonist SB242084 (0.1 and 0.5 microg) immediately prior to testing. The results show that intra-NAc infusions of M100907 significantly decrease impulsive responding on the 5CSRTT and at the highest dose increased omissions as well. By contrast, infusions of SB242084 into the NAc selectively and dose-dependently increased impulsivity. Neither M100907 nor SB242084 significantly altered impulsive responding following either intra-PL or intra-IL administration. However, SB242084 significantly decreased omissions following intra-PL administration (0.5 microg only). These data reveal opposing effects on impulsivity following 5-HT(2A) and 5-HT(2C) blockade in the NAc. Our results suggest that the NAc, but not the PL or IL, is implicated in the mediation of the effects of M100907 and SB242084 on inhibitory response control during baseline 5CSRTT performance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Attention / drug effects
  • Attention / physiology
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Choice Behavior / drug effects
  • Choice Behavior / physiology*
  • Dose-Response Relationship, Drug
  • Fluorobenzenes / pharmacology
  • Impulsive Behavior / metabolism
  • Impulsive Behavior / physiopathology
  • Indoles / pharmacology
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuropsychological Tests
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Piperidines / pharmacology
  • Rats
  • Reaction Time / drug effects
  • Reaction Time / physiology*
  • Receptor, Serotonin, 5-HT2A / drug effects
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Receptor, Serotonin, 5-HT2C / drug effects
  • Receptor, Serotonin, 5-HT2C / metabolism*
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
  • Aminopyridines
  • Fluorobenzenes
  • Indoles
  • Piperidines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Serotonin Antagonists
  • Serotonin
  • volinanserin