GABA release from mouse brain slices following acute and chronic pentobarbital administration and during withdrawal

Ca²⁺-dependent K⁺-stimulated (³H)-γ-aminobutyric acid (GABA) release from mouse striatal and cerebellar slices following acute and chronic pentobarbital administration and during withdrawal was investigated. Acute administration of pentobarbital caused an increase of Ca²⁺-dependent K⁺-stimulated (³H)-GABA release from the striatum, but it did not exert any effect on cerebellum. Spontaneous (³H)-GABA release from the striatum and the cerebellum was not affected by acute pentobarbital treatment. This was further confirmed by the finding that pentobarbital (10^-8-10^-4M) potentiated Ca²⁺-dependent K⁺-stimulated (³H)-GABA release from the striatum, but not from the cerebellum in the in vitro assay. On the other hand, chronic administration of pentobarbital resulted in a decrease of spontaneous (³H)-GABA release and had no effect on Ca²⁺-dependent K⁺-stimulated GABA release from the striatum. The spontaneous release of (³H)-GABA from the striatum remained at significantly lower levels after an abrupt withdrawal from pentobarbital. In pentobarbital withdrawal mice, a decrease of (³H)-GABA release also was observed in the cerebellum. These results strongly suggest that the GABA system in the central nervous system plays an important role in barbiturate narcosis and further links the GABA system with the development of barbiturate tolerance and dependence.