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Molander, A.* ; Vengeliene, V.* ; Heilig, M.* ; Wurst, W. ; Deussing, J.M.* ; Spanagel, R.*

Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking.

Neuropsychopharmacology 37, 1047-1056 (2012)

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Open Access Green as soon as Postprint is submitted to ZB.

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Corticotropin-releasing hormone (CRH) and its receptor, CRH receptor-1 (CRHR1), have a key role in alcoholism. Especially, post-dependent and stress-induced alcohol intake involve CRH/CRHR1 signaling within extra-hypothalamic structures, but a contribution of the hypothalamic-pituitary-adrenal (HPA) axis activity might be involved as well. Here we examined the role of CRHR1 in various drinking conditions in relation to HPA and extra-HPA sites, and studied relapse-like drinking behavior in the alcohol deprivation model (ADE). To dissect CRH/CRHR1 extra-HPA and HPA signaling on a molecular level, a conditional brain-specific Crhr1-knockout (Crhr1(NestinCre)) and a global knockout mouse line were studied for basal alcohol drinking, stress-induced alcohol consumption, deprivation-induced intake, and escalated alcohol consumption in the post-dependent state. In a second set of experiments, we tested CRHR1 antagonists in the ADE model. Stress-induced augmentation of alcohol intake was lower in Crhr1(NestinCre) mice as compared with control animals. Crhr1(NestinCre) mice were also resistant to escalation of alcohol intake in the post-dependent state. Contrarily, global Crhr1 knockouts showed enhanced stress-induced alcohol consumption and a more pronounced escalation of intake in the post-dependent state than their control littermates. Basal intake and deprivation-induced intake were unaltered in both knockout models when compared with their respective controls. In line with these findings, CRHR1 antagonists did not affect relapse-like drinking after a deprivation period in rats. We conclude that CRH/CRHR1 extra-HPA and HPA signaling may have opposing effects on stress-related alcohol consumption. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords alcoholism; stress; relapse; post-dependent drinking; alcohol deprivation effect (ADE); conditional Crhr I nestinCre-knockout mice

ISSN (print) / ISBN 0893-133X

e-ISSN 1470-634X

Journal Neuropsychopharmacology

Quellenangaben Volume: 37, Issue: 4, Pages: 1047-1056

Publisher Nature Publishing Group

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CCG Molecular Neurogenetics (IDG-KMN)