In vitro changes in gamma-aminobutyric acid output from the cerebral cortex induced by inhibitors of gamma-aminobutyric acid uptake and metabolism.

The effects of inhibitors of gamma-aminobutyric acid (GABA) metabolism or uptake on GABA output from the cerebral cortex was studied by means of a collecting cup placed on the exposed cortex of rats anaesthetized with urethane. GABA was identified and quantified by a mass-fragmentographic method. Ethanolamine-O-sulphate (10(-2) M) applied directly on the cerebral cortex caused a long-lasting twofold increase in GABA output, whereas DL-2,4-diaminobutyric acid (5 X 10(-3) M) caused a sevenfold increase and beta-alanine was active. The results indicate that glial uptake has little effect on GABA inactivation in the cerebral cortex. The inhibition of neuronal uptake seems a more effective tool to increase GABA concentration in the synaptic cleft, and consequently also in GABA output, than the inhibition of GABA metabolism.