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

Chronic barbital treatment significant increased the net K+-stimulated uptake of 45Ca2+ in cerebrocortical synaptosomal preparations, 24 h after withdrawal from chronic barbital administration. Basal uptake was not significantly changed. Hippocampal synaptosomal preparations showed a similar pattern, but the increase was not significant. The synaptosomal Ca2+ uptake was not affected by incubation with the dihydropyridine Ca2+ channel antagonist, nitrendipine, in controls or after chronic barbital treatment. Acute administration of a single dose of barbital did not alter the basal or stimulated uptake of 45Ca2+ in cortical synaptosomes, when this was measured 36 h after the barbital administration. Hippocampal slices prepared 24 h after withdrawal from chronic barbital treatment showed a significant increase in K+-stimulated uptake of 45Ca2+, and the basal uptake was significantly decreased. Both changes were prevented by nitrendipine. An increase in the density of dihydropyridine-sensitive binding sites was found in the cerebral cortex. The results indicate that both dihydropyridine-sensitive and insensitive neuronal Ca2+ channels are altered by chronic barbiturate treatment. These changes may be involved in physical dependence on barbiturates.