Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress
| Autor: | Karl Björk, Roberto Ciccocioppo, Maurizio Massi, Anton Terasmaa, Andrea Cippitelli, Ac Hansson, Wh Sommer, Amalia Fedeli, Markus Heilig, Laura Soverchia |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Genotype In situ hybridization Biology Receptors Corticotropin-Releasing Hormone Rats Mutant Strains Recurrence Stress Physiological Internal medicine Gene expression medicine Animals Genetic Predisposition to Disease Antalarmin Rats Wistar Receptor Multidisciplinary Behavior Animal Antagonist Genetic Variation Biological Sciences Phenotype Rats Alcoholism Endocrinology Hormone receptor medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:15236-15241 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0604419103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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