Presnyaptic noradrenergic regulation during depression and antidepressant drug treatment

A specific testable hypothesis in which supersensitive α-2- adrenoreceptors play an important role in the etiology and maintenance of affective illness is presented based on the following observations: (1) published findings of changes in adrenergic receptors in the periphery and brains of rats in response to antidepressant regimens; (2) new studies of the monoamine oxidase type A- inhibiting antidepressant clotgyline, specifically relating to adaptation in the α- adrenergic presynaptic negative feedback system; (3) human peripheral α-adrenergic receptor changes from studies of patients with affective illness; and (4) observations from animals and humans experiencing stress and withdrawal from chronic amphetamine and opiate administration, suggesting that the development of supersensitive α-2-adrenoreceptors may lead to affective illness in vulnerable individuals. Old and new pharmacologic treatments are then discussed in terms of their capacity to specifically alter adrenergic receptor state.