Effects of pentobarbital in mice selected for differential sensitivity to ethanol.

Two lines of mice have been genetically selected for differential sensitivity to ethanol. These lines have been designated long sleep (LS) and short sleep (SS) on the basis of their hypnotic response to the ethanol selection dose. Earlier studies of these mice suggested that this difference was limited to alcohols and did not extend to other classes of hypnotics. The present study examined hypnotic and hypothermic responses produced by pentobarbital in recent generations of these mice. Dose-dependent differences in sleep time and in hypothermia were found, with SS mice affected to a greater degree than LS mice. Pharmacokinetic studies showed that the half-life of pentobarbital disappearence from SS blood was twice that reported for SS mice of the 18th generation. The half-life in the LS line had not changed. The volumes of distribution and waking brain concentrations were identical in LS and SS mice. An altered rate of elimination (not differential CNS sensitivity) appeared to be the major factor responsible for the differences observed between these lines.