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  • Title: Acute and chronic effects of barbituartes on depolarization-induced calcium influx into rat synaptosomes.
    Author: Leslie SW, Friedman MB, Wilcox RE, Elrod SV.
    Journal: Brain Res; 1980 Mar 10; 185(2):409-17. PubMed ID: 7357435.
    Abstract:
    Depolarization-induced 45Ca2+ influx into synaptosomes isolated from nontreated control and acutely treated rats (given 60 mg/kg phenobarbital i.p.) was significantly depressed (54 and 37%, respectively) by an in vitro challenge with pentobarbital, 0.3 mM (final concentration). However, depolarization-induced 45Ca2+ influx into synaptosomes isolated from tolerant rats (received dietary phenobarbital, 2.5 mg/g of diet, for 13 days) was not significantly altered when the synaptosomes were challenged with 0.3 mM pentobarbital. This suggests that synaptosomal membranes adapt during chronic exposure to barbiturates to allow for an enhanced Ca2+ influx subsequent to depolarization. Our data suggest that sedation may, at least in part, occur as a result of depressed stimulus-secretion coupling and that behavioral tolerance to sedation may occur because of the development of membrane tolerance to allow enhanced calcium influx.
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