Abstract

Male Sprague-Dawley rats (250--300 g) were randomly divided into three experimental groups: control, acute (received a single dose of 60 mg/kg of phenobarbital i.p.) and tolerant (received dietary phenobarbital, 2.5 mg/kg of milled Purina Lab Chow, for 13 days). Cerebral cortex (CT), cerebellum (CB), brain stem (BS), striatum (ST), hypothalamus (HT), and mid-brain (MB) were isolated, and the inhibitory effects of barbiturates on KCl-induced 45Ca++ influx into synaptosomes from each of these brain regions isolated from each experimental group were examined. KCl-induced 45Ca++ influx into CT, CB and BS synaptosomes from control animals was significantly depressed (39, 73 and 77% respectively) by an in vitro pentobarbital (0.3 mM) challenge. No significant depression of 45Ca++ influx was produced by pentobarbital in control synaptosomes isolated from ST, HT or MB. KCl-induced 45Ca++ influx into synaptosomes from tolerant rats was not significantly depressed by the in vitro pentobarbital challenge in any brain area. The results suggest that 45Ca++ influx into synaptosomes from CT, CB and BS is more susceptible than ST, HT and MB to inhibition by barbiturates. In addition, chronic administration of phenobarbital resulted in the adaptation of CT, CB and BS synaptosomes to the inhibitory effects of in vitro pentobarbital. This adaptation occurred in the same time frame as did the development of behavioral tolerance.