Enhanced and Delayed Stress-Induced Alcohol Drinking in Mice Lacking Functional CRH1 Receptors

Author:

Sillaber Inge1,Rammes Gerhard1,Zimmermann Stephan1,Mahal Beatrice1,Zieglgänsberger Walter1,Wurst Wolfgang12,Holsboer Florian1,Spanagel Rainer13

Affiliation:

1. Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.

2. National Research Center for Environment and Health, Institute for Mammalian Genetics, Ingolstädter Landstrasse 1, 85764 Munich, Germany.

3. Central Institute of Mental Health, University of Heidelberg, J5, 68159 Mannheim, Germany.

Abstract

There is a relation between stress and alcohol drinking. We show that the corticotropin-releasing hormone (CRH) system that mediates endocrine and behavioral responses to stress plays a role in the control of long-term alcohol drinking. In mice lacking a functional CRH1 receptor, stress leads to enhanced and progressively increasing alcohol intake. The effect of repeated stress on alcohol drinking behavior appeared with a delay and persisted throughout life. It was associated with an up-regulation of the N -methyl- d -aspartate receptor subunit NR2B. Alterations in the CRH1 receptor gene and adaptional changes in NR2B subunits may constitute a genetic risk factor for stress-induced alcohol drinking and alcoholism.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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