title: Differential effects to CCK-4-induced panic by dexamethasone and hydrocortisone.
abstract: OBJECTIVE
  Peripheral administration of the cholecystokinin (CCK) receptor agonist CCK-4 generates panic and activates the hypothalamic-pituitary-adrenal (HPA) axis. Direct effects at the pituitary and CCK-HPA interactions at higher regulatory sites have been suggested. According to preliminary data, ACTH response to CCK receptor agonists may differ from its response to exogenous CRH by its resistance to cortisol feedback inhibition. To further explore this resistance and to better characterize CCK-4 sites of action, the effects of different glucocorticoid pretreatments on CCK-4-induced panic were compared.
  
  
  METHODS
  Using a double-blind placebo-controlled design we pretreated healthy males with either dexamethasone (peripheral action) or hydrocortisone (central-peripheral action) each followed by a CCK-4 challenge. Blood levels of ACTH and cortisol were analyzed and panic symptoms were assessed.
  
  
  RESULTS
  We found a blunted response of ACTH release following CCK-4 injection only after hydrocortisone pretreatment. Dexamethasone however did not affect CCK-4-induced ACTH release relative to baseline. In contrast to dexamethasone, hydrocortisone reduced the severity of CCK-4-induced panic as measured by the Acute Panic Inventory on a trend level.
  
  
  CONCLUSIONS
  Findings suggest that CCK-4-induced stress hormone release seems susceptible to cortisol-feedback inhibition and argues for a suprapituitary site of CCK action. Effects on panic anxiety were weak but congruent with studies showing that CCK-4-induced HPA axis inhibition is accompanied by a reduction of anxiety after CCK-4.
authors: University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany. c.demiralay@uke.de
authors: Cüneyt
authors: C
authors: Demiralay
authors: Holger
authors: H
authors: Jahn
authors: Michael
authors: M
authors: Kellner
authors: Alexander
authors: A
authors: Yassouridis
authors: Klaus
authors: K
authors: Wiedemann
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008297:Male; D016584:Panic Disorder / Q000139:chemically induced* / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D013758:Tetragastrin / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D013758:Tetragastrin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone