The aim of this study was to examine the effects of subchronic administration of psychoactive drugs on the α subunits of G proteins in the rat brain, and also to determine if different classes of psychoactive drugs share a common property, i.e., of altering levels of these proteins. For this purpose, we selected the psychoactive drugs desipramine and phenelzine (antidepressants), lithium (antimanic), alprazolam and buspirone (anxiolytics), and metachlorophenylpiperazine (anxiogenic). The levels of α subunits of G proteins (G(s), G(i1/2), G(q/11)) expressed in cortical, hippocampal, and cerebellar brain regions were studied by the Western blot technique. We observed that subchronic treatment with lithium significantly decreased, and with phenelzine significantly increased levels of G(i1/2)α protein in the cortex and the hippocampus. On the other hand, buspirone significantly decreased levels of G(i1/2)α protein only in the cerebellum. Other psychoactive drugs, however, namely desipramine, meta-chlorophenylpiperazine, and alprazolam, did not alter levels of G(s), G(il/2), or G(q/11)α proteins in any of the brain regions studied. Since other studies have shown the involvement of G proteins in the mechanism of action of psychoactive drugs, our results demonstrate that expressed protein levels of the α subunit of G proteins are not altered by all the psychoactive drugs.