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Publication : Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice.

First Author  de Fiebre CM Year  1992
Journal  Alcohol Clin Exp Res Volume  16
Issue  3 Pages  511-21
PubMed ID  1352660 Mgi Jnum  J:2775
Mgi Id  MGI:51297 Doi  10.1111/j.1530-0277.1992.tb01409.x
Citation  de Fiebre CM, et al. (1992) Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice. Alcohol Clin Exp Res 16(3):511-21
abstractText  A classical (Mendelian) genetic analysis of responses to eight sedative-hypnotic compounds (ethanol, urethane, trifluoroethanol, chloral hydrate, barbital, paraldehyde, methyprylon, pentobarbital) was conducted in crosses derived from mouse lines that were selectively bred for differential duration of anesthesia following ethanol. The sleep-time responses of these mice, the long-sleep (LS) and short-sleep (SS) mouse lines, as well as the F1, F2 and backcross (F1 x LS, F1 x SS) generations were measured. Generally, differences in responses among the generations were greater for water soluble compounds than were differences for more lipid soluble compounds. Also, the inheritance of responses to water soluble compounds could be explained primarily by additive effects of alleles while the inheritance patterns for more lipid soluble compounds were more complex. Genetic correlation with ethanol response decreased with increasing lipophilicity. These results suggest that the selection of the LS-SS mouse lines was specific for water soluble anesthetic agents. Because several of these agents are known to act at GABA receptors, examination of the interactions of compounds which differ in lipid solubility at GABA receptors from LS and SS mice may prove useful in elucidating the mechanism of the anesthetic actions of ethanol and other drugs.
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