Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors.
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.
Sillaber
Inge
I
Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. sillaber@mpipsykl.mpg.de
Rammes
Gerhard
G
Zimmermann
Stephan
S
Mahal
Beatrice
B
Zieglgänsberger
Walter
W
Wurst
Wolfgang
W
Holsboer
Florian
F
Spanagel
Rainer
R
D000200:Action Potentials; D000428:Alcohol Drinking; D000437:Alcoholism / Q000209:etiology* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D000431:Ethanol / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009154:Mutation; D018091:Receptors, AMPA / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000503:physiopathology; D013315:Stress, Psychological / Q000503:physiopathology*; D015854:Up-Regulation; D000099052:CRF Receptor, Type 1
D003346:Corticotropin-Releasing Hormone; D000431:Ethanol; D018091:Receptors, AMPA; D018019:Receptors, Corticotropin-Releasing Hormone; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D000099052:CRF Receptor, Type 1; C121001:NR2B NMDA receptor