A critical role for the cannabinoid CB1 receptors in alcohol dependence and stress-stimulated ethanol drinking.
Although many people drink alcohol regularly, only some become addicted. Several studies have shown that genetic and environmental factors contribute to individual differences in the vulnerability to the effects of alcohol (Nestler, 2000; Kreek, 2001; Crabbe, 2002). Among the environmental factors, stress is perhaps the most important trigger for relapse after a period of abstinence (Koob and Nestler, 1997; Piazza and Le Moal, 1998; Koob and Le Moal, 2001; Weiss et al., 2001). Here we show that ethanol withdrawal symptoms were completely absent in cannabinoid CB1 receptor-deficient mice, although acute effects of ethanol and ethanol tolerance and preference were basically normal. Furthermore, foot-shock stress had no affect on alcohol preference in Cnr1-/- mice, although it induced a dramatic increase in Cnr1+/+ animals. These results reveal a critical role for the CB1 receptor in clinically important aspects of alcohol dependence and provide a rationale for the use of CB1 receptor antagonists in the treatment of alcohol addiction.
Racz
Ildiko
I
Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, 53105 Bonn, Germany.
Bilkei-Gorzo
Andras
A
Toth
Zsuzsanna E
ZE
Michel
Kerstin
K
Palkovits
Miklós
M
Zimmer
Andreas
A
D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D001259:Ataxia / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D004597:Electroshock; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced; D007069:Ifosfamide; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016685:Mitomycin; D009043:Motor Activity / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency* / Q000235:genetics; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000172:deficiency* / Q000235:genetics; D013312:Stress, Physiological; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014751:Vindesine
C578453:CNR1 protein, mouse; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000431:Ethanol; D016685:Mitomycin; D002945:Cisplatin; D014751:Vindesine; D007069:Ifosfamide