Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen

Jianping Chen, William Paredes, Herman M. van Praag, Eliot L. Gardner

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Clozapine alters mesolimbic dopamine (DA) function but spares nigrostriatal DA function in laboratory animals, but the underlying mechanism is unknown. In the present study, acute intraperitoneal injection of clozapine (5-40 mg/kg) increased extracellular DA levels in nucleus accumbens (Acb) and caudate-putamen (CPu) of awake, freely moving rats as measured by in vivo brain microdialysis, without anatomic selectivity. However, in serotonin (5HT)-denervated rats acute clozapine preferentially enhanced DA levels in Acb as compared to CPu. Since (i) up-regulation of 5HT receptors on DA neurons may result from 5HT denervation, (ii) clozapine has potent anti-5HT action, and (iii) 5HT receptors are more dense in Acb than CPu, these data appear to add additional weight to previous suggestions that a serotonergic mechanism may partly underlie clozapine's mesolimbic selectivity.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
JournalBrain Research
Volume582
Issue number1
DOIs
StatePublished - Jun 5 1992

Keywords

  • 5-Hydroxytryptamine
  • Antipsychotic
  • Caudate-putamen
  • Clozapine
  • Dopamine
  • Mesolimbic
  • Microdialysis
  • Neuroleptic
  • Nigrostriatal
  • Nucleus accumbens
  • Serotonin

ASJC Scopus subject areas

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

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