title: Role of prefrontal cortex glucocorticoid receptors in stress and emotion.
abstract: BACKGROUND
  Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation.
  
  
  METHODS
  We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field.
  
  
  RESULTS
  The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyperlocomotion in the open field, but did not affect stress sensitization or helplessness behavior.
  
  
  CONCLUSIONS
  The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: McKlveen
authors.forename: Brent
authors.initials: B
authors.lastname: Myers
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Flak
authors.forename: Jana
authors.initials: J
authors.lastname: Bundzikova
authors.forename: Matia B
authors.initials: MB
authors.lastname: Solomon
authors.forename: Kim B
authors.initials: KB
authors.lastname: Seroogy
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000339:Affect / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000235:genetics / Q000503:physiopathology*; D004644:Emotions / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000502:physiology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics / Q000503:physiopathology*
chemical_list: D034741:RNA, Small Interfering; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Depression-like behavior; HPA axis; glucocorticoid receptor; prefrontal cortex; rat; stress