The effects of kainic acid lesions on dopaminergic responses to haloperidol and clozapine

Mark E. Bardgett*, Sheryl L. Salaris, Jamie L. Jackson, John Harding, John G. Csernansky

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The antipsychotic drugs haloperidol and clozapine have the common action of increasing dopamine metabolism in the striatum (nucleus accumbens, caudate-putamen) of the rat. Intracerebroventricular administration of kainic acid (KA) produces neuronal loss in limbic-cortical brain regions which project directly or indirectly to the striatum. In the present study, dopamine metabolism in subregions of the striatum was examined in rats with KA lesions after acute and chronic haloperidol or clozapine administration. The main findings was that the elevating effect of acute haloperidol treatment on the dopamine metabolite, DOPAC, was blocked in the nucleus accumbens shell and diminished in medial and laterodorsal caudate-putamen of the KA-lesioned rats. In addition, the elevating effects of both acute and chronic haloperidol treatment on dopamine turnover were attenuated in the laterodorsal caudate-putamen of KA-lesioned rats. The levels of dopamine, DOPAC, and HVA after chronic clozapine treatment were greater in KA-lesioned than control rats. These results indicate that dopaminergic responses to haloperidol may be diminished by limbic-cortical neuropathology, while such pathology does not significantly alter dopaminergic responses to clozapine.

Original languageEnglish (US)
Pages (from-to)142-151
Number of pages10
JournalPsychopharmacology
Volume133
Issue number2
DOIs
StatePublished - Oct 6 1997

Keywords

  • 3,4-Dihydroxyphenylacetic acid
  • Antipsychotic
  • Caudate-putamen
  • D receptors
  • Dopamdine
  • Hippocampus
  • Homovanillic acid
  • Kainic acid
  • Nucleus accumbens

ASJC Scopus subject areas

  • Pharmacology

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