Nature Genetics
14, 98 - 101 (1996)
doi:10.1038/ng0996-98
Elevated alcohol consumption in null mutant mice lacking 5−HT1B serotonin receptorsJohn C. Crabbe1, 3, Tamara J. Phillips1, Daniel J. Feller1, René Hen2, Charlotte D. Wenger1, Christina N. Lessov1
& Gwen L. Schafer1
1Department of Veterans Affairs Medical Center and Oregon Health Sciences University, Research Service (151W), Portland, Oregon 97201, USA
2Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA
3Correspondence should be addressed to J.C.C. Substantial evidence links alcohol drinking and serotonin (5-HT) functioning in animals1. Lowered central 5-HT neurotransmission has been found in a subgroup of alcoholics, possibly those with more aggressive, assaultive tendencies2. Several rodent studies3 have also suggested that intact 5-HT systems are important determinants of sensitivity and/or tolerance to ethanol-induced ataxia and hypothermia. Null mutant mice lacking the 5-HT1B receptor gene (5-HT1B
−/−) have been developed4 that display enhanced aggression5 and altered 5-HT release in slice preparations from some, but not all, brain areas6. We characterized these mice for sensitivity to several effects of ethanol. Mutant mice drank twice as much ethanol as wild-type mice, and voluntarily ingested solutions containing up to 20% ethanol in water. Their intake of food and water, and of sucrose, saccharin and quinine solutions, was normal. Mutants were less sensitive than wild-types on a test of ethanol-induced ataxia and, with repeated drug administration, tended to develop tolerance more slowly. In tests of ethanol withdrawal and metabolism, mutants and wild-type mice showed equivalent responses. Our results suggest that the 5-HT1B receptor participates in the regulation of ethanol drinking, and demonstrate that serotonergic manipulations lead to reduced responsiveness to certain ataxic effects of ethanol without affecting dependence.
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