Lack of effect of chronic antidepressant treatment on Gs and Gi alpha-subunit protein and mRNA levels in the rat cerebral cortex

Experimental evidence indicates that chronic antidepressant treatment in rats modifies the central nervous system beta-adrenoceptor signaling pathway at multiple sites including receptor, G-protein, adenylyl cyclase, and protein kinase A. In the present study, we examined the postreceptor effect of antidepressant treatment on the protein and mRNA levels of stimulatory and inhibitory G protein alpha-subunits (G alpha(s) and G alpha(i)) and beta-subunits in rats infused continuously with various antidepressants for 21 days. Chronic treatment with tricyclic (desipramine and amitriptyline) and monoamine oxidase inhibiting (tranylcypromine) antidepressants did not significantly affect the immunoreactivity levels of G alpha(s) (both 45- and 52-kDa species), G alpha(i1), G alpha(i2), G beta(36) and beta(35) in rat cerebral cortex. similarly, the levels of mRNA encoding these G protein subunits remained unchanged subsequent to these drug treatments. In contrast, cortical beta-adrenoceptor number was significantly decreased by these treatments. these results suggest that the adaptive changes of rat cerebral cortical beta-adrenoceptor-adenylyl cyclase system often seen after chronic antidepressant treatment are not accompanied by changes in the abundance and gene expression of G alpha(s), G alpha(i), or G beta proteins.