[Antidepressant drugs and beta-adrenergic receptors]

In the late 1970s, it was shown that the repeated administration of antidepressant drugs (AD) caused a decrease in the beta-agonist-stimulated production of cyclic AMP in rat brain slices. This finding was followed by reports showing that treatment with AD for several days reduced the beta-adrenergic receptor density in rat cerebral cortex. The chronological parallel between such phenomenon and the clinical efficacy of these drugs suggests that AD-induced changes of beta-receptor function may play some role as the underlying mechanism of action of AD. In order to elaborate this hypothesis, the biochemical and behavioral effects of AD should be investigated in more detail. We found that (1) behavioral activation by repeated doses of AD was paralleled by a reduction of brain beta-adrenergic receptor binding in the rat cortex; (2) in vivo or in vitro exposure of AD reduced the effect of alpha 2-agonist and beta-agonist on cyclic AMP accumulation in cerebral cortical slices; (3) a large dose (greater than 100 cortical slices; (3) a large dose (greater than 100 microM) of AD directly reduced GTP or F-stimulated adenylate cyclase activity in rat cortical membrane. These evidences were discussed with relation to the mechanism of action of AD.