Is there a relationship between the involvement of extrapyramidal and mesolimbic brain areas with the cataleptic action of neuroleptic agents and their clinical antipsychotic effect?

The electrolytic brain lesion technique was used in the rat to disrupt the ascending dopaminergic pathways to the extrapyramidal (striatal) and mesolimbic brain areas in the lateral hypothalamus and the pathways to the mesolimbic areas only in the rostral hypothalamus. The cataleptic effects of the neuroleptic agents spiroperidol and perphenazine were enhanced in the acute stage following the lateral hypothalamic lesions but were unmodifield or reduced by the rostral hypothalamic lesions. The cataleptic effects of the neuroleptic agents AHR 2277 and thioridazine were not significantly modified in the acute stage by either lesions. Both lateral and rostral hypothalamic lesions markedly reduced or abolished the cataleptic ability of all neuroleptics tested in the chronic stage. The cataleptic activities of the non-neuroleptic agents metoclopramide and bulbocapnine were unmodified or potentiated by lesions in the lateral hypothalamus and potentiated or unmodified by lesions in the rostral hypothalamus respectively during the acute stage. In the chronic stage the cataleptic effects of both agents were markedly reduced or abolished in animals with lateral or rostral hypothalamic lesions. [ABSTRACT FROM AUTHOR]