Alpha-1-noradrenergic neurotransmission, corticosterone, and behavioral depression

Background: Impaired brain alpha-1 noradrenergic neurotransmission has been implicated in some of the symptoms of depressive illness but has been diff icult to investigate experimentally because of the insensitivity of current animal models of depression. The present experiment addressed this problem by examining the effects of pharmacologic blockade and corticosteroid-indu ced desensitization of alpha-1 receptors on two newer, more sensitive model s in mice: the inhibition of nest-leaving and the tail suspension tests (TS T). Methods: Male mice were administered either prazosin, betaxolol, atipamezol e, corticosterone, or repeated restraint stress prior to measurement of eit her nest-leaving or TST General behavioral function was assessed in horizon tal wire, swim, and latency to escape footshock tests. Results: Prazosin increased depressive behavior in the nest-leaving and TST s, whereas corticosterone and restraint stress did so only in the more sens itive nest-leaving test. Betaxolol also reduced nest-leaving, suggestive of an alpha-1 beta-1 receptor synergy. The effects of these agents could not be attributed to hypotension, sedation, or general behavioral impairment Conclusions: The fact that a reduction in alpha-1 noradrenergic neurotransm ission increases depressive behavior, coupled with the fact that this chang e can result from elevated corticosteroid secretion, provides further suppo rt for a role of this factor in depressive illness. As not all alpha-1 func tions are reduced in depression, it is likely that only a subgroup or speci fic locality of alpha-1 receptors are affected. (C) 1999 Society of Biologi cal Psychiatry.