THE EFFECTS OF KAINIC ACID LESIONS ON DOPAMINERGIC RESPONSES TO HALOPERIDOL AND CLOZAPINE

The antipsychotic drugs haloperidol and clozapine have the common acti on of increasing dopamine metabolism in the striatum (nucleus accumben s, caudate-putamen) of the rat. Intracerebroventricular administration of kainic acid (KA) produces neuronal loss in limbic-cortical brain r egions which project directly or indirectly to the striatum. In the pr esent study, dopamine metabolism in subregions of the striatum was exa mined in rats with KA lesions after acute and chronic haloperidol or c lozapine administration. The main findings was that the elevating effe ct of acute haloperidol treatment on the dopamine metabolite, DOPAC, w as blocked in the nucleus accumbens shell and diminished in medial and laterodorsal caudate-putamen of the KA-lesioned rats. In addition. th e 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 chr onic clozapine treatment were greater in KA-lesioned than control rats . These results indicate that dopaminergic responses to haloperidol ma y be diminished by limbic-cortical neuropathology, while such patholog y does not significantly alter dopaminergic responses to clozapine.