title: Alpha-1-noradrenergic neurotransmission, corticosterone, and behavioral depression.
abstract: BACKGROUND
  Impaired brain alpha-1 noradrenergic neurotransmission has been implicated in some of the symptoms of depressive illness but has been difficult 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-induced desensitization of alpha-1 receptors on two newer, more sensitive models in mice: the inhibition of nest-leaving and the tail suspension tests (TST).
  
  
  METHODS
  Male mice were administered either prazosin, betaxolol, atipamezole, corticosterone, or repeated restraint stress prior to measurement of either nest-leaving or TST. General behavioral function was assessed in horizontal wire, swim, and latency to escape footshock tests.
  
  
  RESULTS
  Prazosin increased depressive behavior in the nest-leaving and TSTs, whereas corticosterone and restraint stress did so only in the more sensitive 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 neurotransmission increases depressive behavior, coupled with the fact that this change can result from elevated corticosteroid secretion, provides further support for a role of this factor in depressive illness. As not all alpha-1 functions are reduced in depression, it is likely that only a subgroup or specific locality of alpha-1 receptors are affected.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, NY, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Stone
authors.forename: D
authors.initials: D
authors.lastname: Quartermain
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects*; D015784:Betaxolol / Q000008:administration & dosage; D003345:Corticosterone / Q000008:administration & dosage*; D003863:Depression / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000008:administration & dosage; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism*; D012149:Restraint, Physical / Q000009:adverse effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D018377:Neurotransmitter Agents; D018340:Receptors, Adrenergic, alpha-1; C050701:atipamezole; D015784:Betaxolol; D003345:Corticosterone; D009638:Norepinephrine; D011224:Prazosin