Inhibition of GABA Metabolism in Rat Brain Slices by Halothane

Abstract

Based on studies with rat cerebral cortex slices, it was hypothesized that halothane anesthesia may result from increased GABA content in the synapses. As GABA is an inhibitory neurotransmitter, such increases may cause a reduction in synaptic activity. The increase in GABA content could arise from several possible causes which are examined in this study using rat cerebral cortex slices as a model. The effects of halothane on uptake, release and catabolism of GABA were determined. Uptake was studied by the amounts of radioactive GABA accumulated by the slices, and release was studied by that discharged into the medium from slices preloaded with radioactive GABA. Catabolism was assessed by preloading the slices with radioactive GABA and then followed by measuring the amount of radioactivity found in unmetabolized GABA or in pooled GABA metabolites. As CO2 was established as a major metabolite, it was subsequently used alone to measure the inhibition of GABA catabolism in the presence of varying amounts of halothane. Halothane (3%) did not affect the high-affinity uptake or release of GABA but did inhibit the catabolism of GABA. Using 14CO2 production as an index of catabolism, the inhibition of GABA catabolism by halothane was dose-related (8.79% inhibition/% halothane). Such results support the hypothesis that halothane anesthesia may be due to an inhibition of GABA catabolism which causes increased GABA level in the synapse with resultant synaptic inhibition.