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Science 296 (5569): 931-933

Copyright © 2002 by the American Association for the Advancement of Science

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

Inge Sillaber,1*dagger Gerhard Rammes,1* Stephan Zimmermann,1 Beatrice Mahal,1 Walter Zieglgänsberger,1 Wolfgang Wurst,12 Florian Holsboer,1 Rainer Spanagel13

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.

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.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: sillaber{at}mpipsykl.mpg.de



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