Faculty Collaboration Database

The effects of kainic acid lesions on dopaminergic responses to haloperidol and clozapine. Psychopharmacology (Berl) 1997 Sep;133(2):142-51

Date

10/29/1997

Pubmed ID

9342780

DOI

10.1007/s002130050384

Scopus ID

2-s2.0-0030774494 (requires institutional sign-in at Scopus site)   16 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.

Author List

Bardgett ME, Salaris SL, Jackson JL, Harding J, Csernansky JG

Author

Jeffrey L. Jackson MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Caudate Nucleus
Clozapine
Corpus Striatum
Dopamine
Dopamine Agonists
Haloperidol
Injections, Intraventricular
Kainic Acid
Male
Nucleus Accumbens
Putamen
Rats
Rats, Sprague-Dawley