Effects of Chronic Treatment of Haloperidol and Clozapine on Levels of G-Protein Subunits in Rat Striatum

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Abstract
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 Gproteins in the rat striatum using the Western blot method. Results of the present study demonstrate that the treatment with haloperidol or clozapine, respectively, downregulate or upregulate the levels of G proteins. Quantitative immunoblotting, using sitedirected specific antisera, demonstrated that chronic treatment with haloperidol downregulates Giα, Gsα, and ß subunits while chronic treatment with clozapine upregulates Giα, Gsα, and ß subunits. Neither of these drugs has any effect on the levels of GOα.