• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress.

Alcoholism is a chronic relapsing disorder with substantial heritability. Uncovering gene-environment interactions underlying this disease process can aid identification of novel treatment targets. Here, we found a lowered threshold for stress-induced reinstatement of alcohol seeking in Marchigian-Sardinian Preferring (msP) rats genetically selected for high alcohol preference. In situ hybridization for a panel of 20 stress-related genes in 16 brain regions was used to screen for differential gene expression that may underlie this behavioral phenotype. An innate up-regulation of the Crhr1 transcript, encoding the corticotropin-releasing hormone receptor 1 (CRH-R1), was found in several limbic brain areas of msP rats genetically selected for high alcohol preference, was associated with genetic polymorphism of the Crhr1 promoter, and was accompanied by increased CRH-R1 density. A selective CRH-R1 antagonist (antalarmin, 10-20 mg/kg) was devoid of effects on operant alcohol self-administration in unselected Wistar rats but significantly suppressed this behavior in the msP line. Stress-induced reinstatement of alcohol seeking was not significantly affected by antalarmin in Wistar rats but was fully blocked in msP animals. These data demonstrate that Crhr1 genotype and expression interact with environmental stress to reinstate alcohol-seeking behavior.

Pubmed ID: 17015825

Authors

  • Hansson AC
  • Cippitelli A
  • Sommer WH
  • Fedeli A
  • Bj√∂rk K
  • Soverchia L
  • Terasmaa A
  • Massi M
  • Heilig M
  • Ciccocioppo R

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 10, 2006

Associated Grants

  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Alcoholism
  • Animals
  • Behavior, Animal
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Male
  • Rats
  • Rats, Mutant Strains
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone
  • Recurrence
  • Stress, Physiological