Beta adrenergic receptor function in depression and the effect of antidepressant drugs

It has been suggested that alterations of monoamine receptor sensitivity in the central nervous system may be associated with some forms of affective illness. It has been observed by several investigators that chronic treatment with antidepressant drugs causes down regulation of NE receptor coupled adenylate cyclase and beta adrenergic receptor binding in rat brain. This observation has led to the suggestion that the therapeutic effects of antidepressant drugs may be related to the changes in the responsivity of beta adrenergic receptors. In order to examine if depressive illness may be associated with altered beta adrenergic function, we studied adenylate cyclase and its responsiveness to norepinephrine and isoproterenol in the leukocytes obtained from patients with psychiatric illness and normal controls as an index of beta adrenergic receptor function. We also studied the effects of antidepressant drugs, in vitro, on isoproterenol sensitive leukocyte adenylate cyclase. We observed that norepinephrine and isoproterenol sensitive leukocyte adenylate cyclase in depressed patients are significantly decreased as compared to normal controls. Our results appear to have been replicated by another group of investigators. We also observed that certain antidepressant drugs potentiate isoproterenol stimulated accumulation of cyclic AMP in human leukocytes. This potentiation was most pronounced in the case of iprindole. These results thus indicated a decreased beta adrenergic receptor function in patients with depressive illness. Whether or not such decreased receptor function is associated with depressive illness or is a manifestation of some other changes unrelated to the illness is not clear. Our results also indicate that some antidepressant drugs may enhance adrenergic transmission by potentiating the effects of neurotransmitters on beta adrenergic receptors.