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Classical Genetic Analyses of Responses to Sedative‐Hypnotic Drugs in Crosses Derived from Long‐Sleep and Short‐Sleep Mice
Author(s) -
Fiebre Christopher M.,
Marley Rodney J.,
Miner Lucinda L.,
Fiebre Nancy Ellen C.,
Wehner Jeanne M.,
Collins Allan C.
Publication year - 1992
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1992.tb01409.x
Subject(s) - chloral hydrate , sedative/hypnotic , hypnotic , pentobarbital , anesthetic , barbital , pharmacology , sedative , chemistry , ethanol , biochemistry , biology , anesthesia , medicine
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 × LS, F1 × 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.