Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptors.
Substantial evidence links alcohol drinking and serotonin (5-HT) functioning in animals. Lowered central 5-HT neurotransmission has been found in a subgroup of alcoholics, possibly those with more aggressive, assaultive tendencies. Several rodent studies 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 developed that display enhanced aggression and altered 5-HT release in slice preparations from some, but not all, brain areas. 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.
Crabbe
J C
JC
Department of Veterans, Affairs Medical Center, Portland, Oregon, USA.
Phillips
T J
TJ
Feller
D J
DJ
Hen
R
R
Wenger
C D
CD
Lessov
C N
CN
Schafer
G L
GL
D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000503:physiopathology; D004435:Eating; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D000431:Ethanol