Biometrical genetic analysis of ethanol's psychomotor stimulant effect

Hereditary influences on psychomotor stimulant effects of ethanol (ETOH) were studied in a classical Mendelian cross of DBA/2Abg (D2) and C57BL/6Abg (B6) inbred mouse strains. A dose-response study with nine doses (0-3.5 g/kg ip) indicated that B6 mice lack the activational limb of the biphasic curve (< or = 1.5 g/kg), as assessed in a 15-min test. D2 mice ran greater distances and ran faster, at doses up to 2.5 g/kg. B6 mice showed no increments in speed or distance at these doses that activated D2 mice. Several other indices reinforced the conclusion of ETOH-induced behavioral activation in D2 mice and lack there of in B6 mice (traditional photobeam interruptions--horizontal counts; center distance; vertical movements; inactive time; as well as derived indices of running speed and average length of each movement). The F1, F2, and backcross generations produced dose-response curves that showed additive inheritance of the activational response to doses below 1.5 g/kg. A second study (n = 1446) examined response to 1.5 g/kg with a within-subjects design in the full Mendelian cross. This study verified the completely additive mode of inheritance for the total distance measure suggested in the dose-response study, and showed that sex linkage and sex differences were not present. Narrow sense heritability of the ETOH activation response (indexed by total distance) was calculated at 0.35 and approximately 3 loci were estimated to be responsible for the B6/D2 difference. The other phenotypes (described above) also showed strongly additive genetic control.(ABSTRACT TRUNCATED AT 250 WORDS)