Stimulant and depressant properties of sedative-hypnotics in mice selectively bred for differential sensitivity to ethanol.

A genetic analysis of sedative-hypnotic response in selectively bred Long-Sleep (LS) and Short-Sleep (SS) mice showed LS mice to be more depressed by acetaldehyde, ethanol (ETOH), and t-butanol, but less sensitive to pentobarbital. Intermediate inheritance was shown by the two reciprocal F1 hybrids for the alcohols, but dominance to the LS genotype occurred for the aldehyde and the barbiturate. At several subhypnotic doses of ETOH in two experiments, LS mice showed less locomotor stimulation and greater disruption of coordination than the SS mice. The two reciprocal F1 hybrids did not differ from one another and had dose-response curves intermediate to the two parental lines. Study of the effects of t-butanol on locomotor activity revealed a pattern of line differences similar to that for ETOH. The genetic selection for LS and SS mice appears to have differentiated loci that pleiotropically influence a variety of behavioral responses to alcohols.