Increases in neuronal Ca2+ flux after withdrawal from chronic barbiturate treatment

Chronic barbital treatment significant increased the net K+-stimulated upta ke of Ca-45(2+) in cerebrocortical synaptosomal preparations, 24 h after wi thdrawal from chronic barbital administration. Basal uptake was not signifi cantly changed. Hippocampal synaptosomal preparations showed a similar patt ern, but the increase was not significant. The synaptosomal Ca2+ uptake was not affected by incubation with the dihydropyridine Ca2+ channel antagonis t, nitrendipine, in controls or after chronic barbital treatment. Acute adm inistration of a single dose of barbital did not alter the basal or stimula ted uptake of Ca-45(2+) in cortical synaptosomes, when this was measured 36 h after the barbital administration. Hippocampal slices prepared 24 h afte r withdrawal from chronic barbital treatment showed a significant increase in K+-stimulated uptake of Ca-45(2+), and the basal uptake was significantl y decreased. Both changes were prevented by nitrendipine. An increase in th e density of dihydropyridine-sensitive binding sites was found in the cereb ral cortex. The results indicate that both dihydropyridine-sensitive and in sensitive neuronal Ca2+ channels are altered by chronic barbiturate treatme nt. These changes may be involved in physical dependence on barbiturates. ( C) 1999 Elsevier Science B.V. All rights reserved.