The effect of chronic atypical antipsychotic drugs and haloperidol on amphetamine-induced dopamine release in vivo

Junji Ichikawa, Herbert Y. Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The effect of chronic administration of antipsychotic drugs (21 days in drinking water followed by 3 days drug washout) on the d-amphetamine (1.0 mg/kg, s.c.)-induced increase in dopamine (DA) release in the striatum and the nucleus accumbens of awake, freely-moving rats was investigated with microdialysis. Chronic administration of haloperidol, a typical antipsychotic, (0.5 mg/kg/day), decreased basal extracellular DA release in the striatum and the nucleus accumbens but did not affect d-amphetamine-induced DA release in either region. In marked contrast, chronic administration of three atypical antipsychotic drugs: amperozide (2 mg/kg/day), clozapine (10 mg/kg/day) and melperone (2 mg/kg/day) increased basal extracellular DA and enhanced d-amphetamine-induced DA release in the striatum. In the nucleus accumbens, basal extracellular DA was decreased by chronic amperozide, unchanged by chronic clozapine and increased by chronic melperone. Most significantly, d-amphetamine-induced DA release was inhibited by chronic amperozide or clozapine, but unaffected by chronic melperone in this region. These results suggest that atypical antipsychotic drugs can alter DA release in a region specific manner. In particular, attenuation of amphetamine-like stimulation of DA release with reduced basal DA release in the nucleus accumbens could contribute to the antipsychotic action of amperozide which has a very weak affinity for D2 DA receptors.

Original languageEnglish (US)
Pages (from-to)98-104
Number of pages7
JournalBrain research
Volume574
Issue number1-2
DOIs
StatePublished - Mar 6 1992

Keywords

  • Amperozide
  • Atypical antipsychotic
  • Chronic administration
  • Dopamine metabolism
  • Dopamine release
  • Haloperidol
  • In vivo microdialysis
  • Nucleus accumbens
  • Striatum
  • d-Amphetamine

ASJC Scopus subject areas

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

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