title: Effects of a stressor and corticotrophin releasing factor on ethanol deprivation-induced ethanol intake and anxiety-like behavior in alcohol-preferring P rats.
abstract: BACKGROUND
  Stress may elevate ethanol drinking and anxiety associated with ethanol drinking. Studies to identify relevant neurobiological substrates are needed.
  
  
  OBJECTIVE
  To assess roles of brain regions in corticotrophin releasing factor (CRF) effects on stressor-enhanced, ethanol deprivation-induced drinking and anxiety-like behavior.
  
  
  METHODS
  Ethanol-preferring rats (P rats) were exposed to three cycles of a two-bottle choice paradigm with two 2-day deprivation periods that included 1 h exposure to a restraint stressor. To assess the role of CRF and to identify relevant brain regions, a CRF-1 receptor antagonist (SSR125543; 10 ug) was injected into the nucleus accumbens (NAC), amygdala (Amyg), or dorsal raphe nucleus (DRN) prior to exposure to the restraint stressor. In a second study, CRF (0.5 ug) was injected into one of these regions, or the ventral tegmental area (VTA), or paraventricular nucleus of the hypothalamus (PVN).
  
  
  RESULTS
  Applying the restraint stressor during deprivation increased voluntary intake and sensitized anxiety-like behavior. Antagonist injection into the NAC prevented increased drinking without affecting anxiety-like behavior, whereas injection into the Amyg or DRN prevented the anxiety-like behavior without affecting drinking. To confirm CRF actions in the stressor effect, CRF was injected into selected brain regions. NAC injections (but not the VTA, Amyg, DRN, or PVN) facilitated drinking but did not change anxiety-like behavior. Injections into the DRN or Amyg (but not PVN or VTA) enhanced anxiety-like behavior.
  
  
  CONCLUSIONS
  Results emphasize that a restraint stressor elevates ethanol intake and sensitizes ethanol deprivation-induced anxiety-like behavior through CRF1 receptors in the NAC and Amyg/DRN, respectively.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514-7178, USA. darin_knapp@med.unc.edu
authors.forename: Darin J
authors.initials: DJ
authors.lastname: Knapp
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
authors.forename: Mae
authors.initials: M
authors.lastname: Huang
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Wills
authors.forename: Buddy A
authors.initials: BA
authors.lastname: Whitman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Angel
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Sinnett
authors.forename: George R
authors.initials: GR
authors.lastname: Breese
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001921:Brain / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D006846:Hydrocarbons, Halogenated / Q000494:pharmacology; D008297:Male; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications*; D013843:Thiazines / Q000494:pharmacology; D000099052:CRF Receptor, Type 1
chemical_list: D006846:Hydrocarbons, Halogenated; D018019:Receptors, Corticotropin-Releasing Hormone; C502407:SSR125543; D013843:Thiazines; D000431:Ethanol; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone