5-HT2A receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and inhibits that in the nucleus accumbens in a dose-dependent manner

Jean François Liégeois, Junji Ichikawa*, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Combined serotonin (5-HT)2A and dopamine (DA) D2 blockade has been shown to contribute to the ability of atypical antipsychotic drugs (APDs) to increase DA release in rat medial prefrontal cortex (mPFC). We provide additional support for this hypothesis by examining the effect of the selective 5-HT2A antagonist M100907 plus haloperidol, a potent D2 antagonist APD, on DA release in the mPFC and nucleus accumbens (NAC). Haloperidol (0.01-1.0 mg/kg) produced an inverted U-shaped increase in DA release in the mPFC, with a significant increase only at 0.1 mg/kg. Haloperidol (0.1 and 1.0 mg/kg) significantly increased DA release in the NAC. M100907 (0.1 mg/kg) by itself had no effect on DA release in either region. This dose of M100907 potentiated the ability of low (0.01-0.1 mg/kg), but not high dose (0.3-1.0 mg/kg) haloperidol to increase mPFC DA release, whereas it abolished the effect of both 0.1 and 1.0 mg/kg haloperidol on NAC DA release. These results suggest that the relatively higher ratio of 5-HT2A to D2 antagonism may contribute to the potentiation of haloperidol-induced mPFC DA release, whereas 5-HT2A antagonism can diminish haloperidol-induced NAC DA release, even when combined with extensive D2 antagonism, which may not be synergistic with 5-HT2A antagonism in the mPFC.

Original languageEnglish (US)
Pages (from-to)157-165
Number of pages9
JournalBrain research
Volume947
Issue number2
DOIs
StatePublished - Aug 30 2002

Keywords

  • Catecholamine release

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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