title: Presynaptic noradrenergic regulation during depression and antidepressant drug treatment.
abstract: A specific testable hypothesis in which supersensitive alpha-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 clorgyline, specifically relating to adaptation in the alpha-adrenergic presynaptic negative feedback system; (3) human peripheral alpha-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 alpha-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.
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D009638:Norepinephrine / Q000502:physiology*; D013045:Species Specificity; D013312:Stress, Physiological / Q000150:complications; D013569:Synapses / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents; D009638:Norepinephrine