Psychopharmacology

, Volume 218, Issue 1, pp 179–189

Effects of a stressor and corticotrophin releasing factor on ethanol deprivation-induced ethanol intake and anxiety-like behavior in alcohol-preferring P rats

  • Darin J. Knapp
  • David H. Overstreet
  • Mae Huang
  • Tiffany A. Wills
  • Buddy A. Whitman
  • Robert A. Angel
  • Sarah E. Sinnett
  • George R. Breese
Original Investigation

DOI: 10.1007/s00213-011-2366-5

Cite this article as:
Knapp, D.J., Overstreet, D.H., Huang, M. et al. Psychopharmacology (2011) 218: 179. doi:10.1007/s00213-011-2366-5

Abstract

Rationale

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.

Keywords

Corticotrophin releasing factor Stress Stressor Ethanol Ventral tegmental area Nucleus accumbens Alcohol deprivation Amygdala Paraventricular nucleus Raphe Anxiety-like behavior 

Supplementary material

213_2011_2366_MOESM1_ESM.ppt (2 mb)
Supplemental Figure Legend. Microinjection targeting based on the brain atlas of Paxinos and Watson (2005). See “Methods” in text for coordinate details for each brain region. Red circles represent the ideal center point (anterior-posterior, dorso-ventral, and medial-lateral) based on the coordinates detailed in Table 1. For the schematics at left, dark hatched circles represent approximate outer limits of injections deemed acceptable. Other circles indicate representative locations of injections in regions of experimental groups in which CRF (green circles) or the CRF antagonist (black circles) were active. Numbers in the lower right of each schematic reflect the plate number from the atlas. Photomicrographs representing injection sites for each region appear in the right column. The straight hatched lines in the photomicrographs represent the approximate angle of approach to the sites of interest where darkened dye markings can be seen. a Accumbens, b paraventricular nucleus of the hypothalamus, c amygdala, d ventral tegmental area, e dorsal raphe nucleus (PPT 2.04 mb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Darin J. Knapp
    • 1
    • 2
    • 4
  • David H. Overstreet
    • 1
    • 4
  • Mae Huang
    • 1
  • Tiffany A. Wills
    • 1
    • 2
  • Buddy A. Whitman
    • 1
    • 2
  • Robert A. Angel
    • 1
  • Sarah E. Sinnett
    • 1
    • 5
  • George R. Breese
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Bowles Center for Alcohol StudiesUniversity of North Carolina at Chapel HillChapel HillUSA
  2. 2.Neurobiology CurriculumUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.Neuroscience CenterUniversity of North Carolina at Chapel HillChapel HillUSA
  4. 4.Department of PsychiatryUniversity of North Carolina at Chapel HillChapel HillUSA
  5. 5.Department of PharmacologyUniversity of North Carolina at Chapel HillChapel HillUSA