RGD Reference Report - Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. - Rat Genome Database

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

Authors: Hansson, AC  Cippitelli, A  Sommer, WH  Fedeli, A  Bjork, K  Soverchia, L  Terasmaa, A  Massi, M  Heilig, M  Ciccocioppo, R 
Citation: Hansson AC, etal., Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15236-41. Epub 2006 Oct 2.
RGD ID: 1626233
Pubmed: PMID:17015825   (View Abstract at PubMed)
PMCID: PMC1622806   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0604419103   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Crhr1Ratresponse to electrical stimulus  IMP increased alcohol seeking and consumption in response to stress in the Marchigian¿Sardinian Preferring rat strainRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Crhr1Ratincreased alcohol consumption  IAGP DNA:polymorphism:promoterRGD 
Objects Annotated

Genes (Rattus norvegicus)
Crhr1  (corticotropin releasing hormone receptor 1)


Additional Information