title: Persistent effects of prior chronic exposure to corticosterone on reward-related learning and motivation in rodents.
abstract: BACKGROUND
  Repeated or prolonged exposure to stress has profound effects on a wide spectrum of behavioral and neurobiological processes and has been associated with the pathophysiology of depression. The multifaceted nature of this disorder includes despair, anhedonia, diminished motivation, and disrupted cognition, and it has been proposed that depression is also associated with reduced reward-motivated learning. We have previously reported that prior chronic corticosterone exposure to mice produces a lasting depressive-like state that can be reversed by chronic antidepressant treatment.
  
  
  METHODS
  In the present study, we tested the effects of prior chronic exposure to corticosterone (50 μg/ml) administered to rats or to mice in drinking water for 14 days followed by dose-tapering over 9 days.
  
  
  RESULTS
  The exposure to corticosterone produced lasting deficits in the acquisition of reward-related learning tested on a food-motivated instrumental task conducted 10-20 days after the last day of full dose corticosterone exposure. Rats exposed to corticosterone also displayed reduced responding on a progressive ratio schedule of reinforcement when tested on day 21 after exposure. Amitriptyline (200 mg/ml in drinking water) exposure for 14 days to mice produced the opposite effect, enhancing food-motivated instrumental acquisition and performance. Repeated treatment with amitriptyline (5 mg/kg, intraperitoneally; bid) subsequent to corticosterone exposure also prevented the corticosterone-induced deficits in rats.
  
  
  CONCLUSIONS
  These results are consistent with aberrant reward-related learning and motivational processes in depressive states and provide new evidence that stress-induced neuroadaptive alterations in cortico-limbic-striatal brain circuits involved in learning and motivation may play a critical role in aspects of mood disorders.
authors.affiliation: Department of Psychiatry, Division of Molecular Psychiatry, Ribicoff Research Facilities, Yale University School of Medicine, 34 Park St, New Haven, CT 06508, USA. peter.olausson@yale.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Olausson
authors.forename: Drew D
authors.initials: DD
authors.lastname: Kiraly
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Gourley
authors.forename: Jane R
authors.initials: JR
authors.lastname: Taylor
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009042:Motivation / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D003345:Corticosterone