Barbital-induced cross-tolerance to barbiturates by the intracisternal route of administration.

Male rats receiving 2.4 mg of barbital-sodium intracisternally every 3 hours for 4 injections exhibited a significant decrease in sleeping time over that of control animals when challenged with pentobarbital 17 hours after the last pretreatment. These tolerant animals did not show a significant increase in either (14C)-leucine incorporating activity or hepatic aminopyrine demethylase activity. This intracisternal induced cross tolerance to pentobarbital is apparently not due to hepatic enzyme induction, but may be related to an altered sensitivity of the central nervous system to these agents.