Inhibition of the rate of GABA synthesis in regions of rat brain following a convulsion

Abstract

The rate of synthesis of γ‐aminobutyric acid (GABA) in the cortex, hippocampus and striatum of rat brain was assessed by measuring the linear rate of accumulation of GABA following injection of amino‐oxyacetic acid (AOAA). Five min after a single electrically induced seizure there was a rise in GABA content in these brain regions and an almost total inhibition of the rate of synthesis. Five min after seizure induced by the inhalant convulsant flurothyl there was no rise in GABA content in these brain regions but a similar marked degree of inhibition of GABA synthesis. Two hours after the convulsion the rate of GABA synthesis had returned to control values in all three brain regions. A single convulsion did not alter the glutamic acid decarboxylase activity in these brain regions either in the absence or presence of added co‐factor (pyridoxal phosphate). Evidence for an inhibition of GABA release following a convulsion which may be associated with the inhibition of GABA synthesis is presented in the following paper.

The effect of repeated electroconvulsive shock on GABA synthesis and release in regions of rat brain

“…Justification for the use of the method for GABA synthesis measurement has been presented in a preceding paper (Green et al, 1987a (Green et al, 1987a). The degree of synthesis inhibition observed in the striatum in the current study is, in percentage terms, remarkably similar to that observed by the mass fragmentographic approach and extends the previous study by showing that a similar inhibition occurs in the hippocampus.…”

“…The results were obtained by use of the technique of gas chromatography-mass spectrometry (mass fragmentography, Bertillson & Costa, 1976); however, methodological strictures including the precursor-product assumptions inherent in measuring turnover by infusion oflabelled precursors (see Bertillson & Costa, 1976) precluded the use of the method in examining turnover in brain areas such as the cortex and hippocampus. A later study by Bowdler et al (1983) confirmed and extended the observations that the GABA concentration changes in various brain regions following repeated ECS, but did not measure 'Author for correspondence; present address: Astra Neuro- The current studies have demonstrated that a single ECS or flurothyl-induced convulsion can induce marked changes in both GABA synthesis (Green et al, 1987a) and release (Green et al, 1987b) in regions of rat brain. An investigation has therefore been made of the effect of repeated seizures on GABA release in regions ofrat brain and on the rate ofGABA synthesis in various brain regions, the latter study being designed to try to confirm and extend an earlier investigation (Green et al, 1978) by use of a different methodology.…”

The modulation by chlormethiazole of the GABAA‐receptor complex in rat brain

“…The synthesis of GABA in the cortex, hippocampus and striatum was assessed by measuring the accumulation of GABA following an injection of aminooxyacetic acid (AOAA), a method recently described and validated by Green et al (1987). Briefly, animals were injected with chlormethiazole (35mg kg-', i.p.…”

GABAergic dysfunction in mood disorders

“…271 Particularly, it exerts antidepressant and antimanic effectiveness in resistant mood disorder patients. ECT acutely decreased GABA release or GABA synthesis in rat brain 272,273 and plasma GABA levels in depressed patients. 130 On the contrary, with repeated ECT, increases in GABA release, GABA concentration, and GABA B biding sites have been reported in rat brain.…”