beta-Adrenergic receptor regulation and antidepressants: the influence of adrenocorticotropin

Chronic administration of antidepressants reduces brain beta-adrenergic receptor number and function. Peptide and steroid hormones are also capable of modifying receptor activity, and because circulating levels of these substances are altered in depressed patients, studies have been undertaken to determine whether hormones influence the neurochemical responses to antidepressant drugs. Co-administration of adrenocorticotropin (ACTH) and imipramine induces a more rapid reduction in brain beta-adrenergic receptor binding than is observed with either substance alone. Moreover, by itself, ACTH treatment alters the ability of norepinephrine to stimulate cAMP accumulation in brain tissue without affecting recognition site number. Lesioning of the dorsal noradrenergic bundle blocks the decline in beta-receptor number and activity produced by the ACTH-imipramine treatment. Indeed, administration of ACTH facilitated these increase in beta-receptor number that occurs following denervation. These data indicate that ACTH treatment influences beta-adrenergic receptor adaptations that occur in response to a change in synaptic activity. Such findings have implications in regard to the clinical responses to antidepressants, and the role of hormones in the etiology of affective illness.