Effects of chronic treatment of haloperidol and clozapine on levels of G-protein subunits in rat striatum.

Chronic administration of typical neuroleptic drugs, such as haloperidol, causes the supersensitivity of brain dopamine D2 receptor in striatum and limbic regions, while the atypical neuroleptic clozapine does not. In order to understand the mechanism of their action at a molecular level, studies were carried out to assess the effects of chronic treatment of these drugs on the levels of G-proteins in the rat striatum using the Western blot method. Results of the present study demonstrate that the treatment with haloperidol or clozapine, respectively, down-regulate or up-regulate the levels of G proteins. Quantitative immunoblotting, using site-directed specific antisera, demonstrated that chronic treatment with haloperidol down-regulates Gi alpha, Gs alpha, and beta subunits while chronic treatment with clozapine upregulates Gi alpha, Gs alpha, and beta subunits. Neither of these drugs has any effect on the levels of Go alpha.