Pentobarbital distribution in discrete brain areas of tolerant and nontolerant mice

Uptake and distribution of pentobarbital in tolerant and nontolerant mice were studied. Mice were implanted with pentobarbital or placebo pellets s.c. 3 days prior to the injection of 60 mg/kg sodium pentobarbital i.p. One group of animals was sacrificed when they first awakened. Whole brain, five discrete brain areas, and plasma were assayed for pentobarbital by gas chromatography. In a second group, time studies were performed on brain sections and plasma. In tolerant vs nontolerant animals, sleeping time was markedly decreased (10-20 vs 50-70 min); whole brain, brain sections, and plasma levels on awakening were not significantly different; linear and exponential curves of pentobarbital levels vs time showed an increase in slope (-1.05 vs-0.40) and a decrease in T 1/2 (10.2 VS 35.7 min). These findings suggest that the tolerance development to pentobarbital in the central nervous system is due to functional mechanism rather than brain dispositional mechanism.