Differential effects of chronic antipsychotic drug treatment on extracellular glutamate and dopamine concentrations

Bryan Yamamoto, Mary Ann Cooperman

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

Typical and atypical antipsychotic drugs have been reported to affect basal dopaminergic activity differentially in nigrostriatal and limbic structures after acute and chronic administration in animals. In addition, glutamate has been implicated in the pathophysiology of schizophrenia. The purpose of this study was to examine basal and locally stimulated glutamate and dopamine efflux in the caudate, nucleus accumbens, and medial prefrontal cortex using in vivo microdialysis after chronic clozapine and haloperidol treatment. Basal extracellular concentrations of dopamine in the caudate and nucleus accumbens were not different between the drug treatment groups; however, dopamine concentrations were higher in the medial prefrontal cortex after chronic clozapine treatment. Depolarization-induced dopamine release with 80 mM K+ in all three brain regions was attenuated by haloperidol treatment. In contrast, basal concentrations of extracellular glutamate were markedly higher in the caudate and modestly increased in the nucleus accumbens but not in the prefrontal cortex after chronic haloperidol. Chronic clozapine treatment did not have an effect in any of the brain regions examined. K+-stimulated glutamate efflux was unaffected by haloperidol or clozapine in the caudate or prefrontal cortex; however, stimulated glutamate release in the nucleus accumbens was enhanced by clozapine. These data are suggestive of a depolarization inactivation of dopamine nerve terminals in striatum and cortex as revealed by an attenuation of local K+-induced stimulation of dopamine efflux. These results also provide new evidence for a role of glutamate in discriminating the neurochemical effects of chronic treatment with antipsychotic drugs.

Original languageEnglish (US)
Pages (from-to)4159-4166
Number of pages8
JournalJournal of Neuroscience
Volume14
Issue number7
StatePublished - Jul 1994
Externally publishedYes

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Clozapine
Antipsychotic Agents
Glutamic Acid
Dopamine
Nucleus Accumbens
Haloperidol
Prefrontal Cortex
Caudate Nucleus
Microdialysis
Brain
Schizophrenia
Pharmaceutical Preparations

Keywords

  • antipsychotics
  • cortex
  • dopamine
  • glutamate
  • microdialysis
  • striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential effects of chronic antipsychotic drug treatment on extracellular glutamate and dopamine concentrations. / Yamamoto, Bryan; Cooperman, Mary Ann.

In: Journal of Neuroscience, Vol. 14, No. 7, 07.1994, p. 4159-4166.

Research output: Contribution to journalArticle

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