Abstract
The effects on the adenylyl cyclase (AC) system of chronic administration of selective serotonin reuptake inhibitors (SSRIs) and trazodone were examined in rat brain. These drugs have a structure and site of action that differ from those of tricyclic antidepressants. After 21 days of treatment with tricyclic antidepressants, trazodone, and SSRIs, GppNHp-stimulated AC activity was increased in a dose-dependent manner in rat cerebral cortex membranes. In contrast to GppNHp-stimulated AC activity, no significant changes in MnCl2 (20 mM)-stimulated activity were observed between the control and the antidepressant-treated groups. These results suggest that the increase in guanine nucleotide-stimulated AC activity is caused by the activation of Gs and that elevation of cellular cyclic AMP levels through the activation of Gs is a common mechanism of action of antidepressants.
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