Inhibition of GABA release from slices prepared from several brain regions of rats at various times following a convulsion

Abstract

A method is described for the measurement of the K+‐evoked release of endogenous γ‐aminobutyric acid (GABA) from slices of rat cortex, hippocampus and striatum. In tissue prepared 30 min following an electroconvulsive shock, K+‐evoked GABA release (above basal release) was inhibited by 45% in cortex, 50% in hippocampus and 75% in striatum. A similar inhibition of release was observed with slices prepared from rats in which a convulsion had been induced by flurothyl. There was no change in spontaneous (basal) release following either procedure. An inhibition of K+‐evoked endogenous GABA release was also seen in tissue prepared 4 min postictally but not 2 h after the seizure. No difference was observed in the release of [3H]‐GABA from preloaded cortical slices prepared from rats given a single electroconvulsive shock. It is proposed that a convulsion results in an inhibition of GABA release and that this inhibition may in turn inhibit GABA synthesis as described in the preceding paper. It is also proposed that changes in the endogenous releasable pool of GABA may not be detected by preloading slices with [3H]‐GABA.

The effects of single and repeated electroconvulsive shock administration on the release of 5‐hydroxytryptamine and noradrenaline from cortical slices of rat brain

“…The K+-evoked release of endogenous 5-HT and NA from slices of frontal cortex was also not statistically different for either group. These data agree with the previous work of Minchin et al (1983) The principal significance of the data obtained after a single ECS in this study, is that a normal K+-evoked release of endogenous NA and 5-HT was demonstrated at a time after a single ECS when the release of endogenous GABA was significantly inhibited (Green et al, 1987b). These results would tend to indicate the selectivity of the changes in GABAergic biochemistry following ECS, since the inhibition of endogenous GABA release does not appear to be merely a reflection of a more widespread inhibition of transmitter release in the rat brain.…”

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

“…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.…”

“…In contrast, release has returned to control values 2 h after a single ECS (Green et al, 1987b). This prolonged inhibition of striatal function following chronic ECS may reflect the very large inhibition of evoked GABA release seen with a single ECS, being of the order of a 75% inhibition of the evoked release of GABA over spontaneous efflux from the slices (compared with control values), and larger than any other area examined.…”

“…However, using a superfusion system for the estimation of release of GABA from slices preloaded with [3HJ-GABA did not demonstrate any change (Green et al, 1987b) suggesting that release from preloaded slices might not be measuring release from the endogenous pool. The endogenous GABA release system was therefore chosen to investigate the release of GABA at two time points after chronic ECS treatment.…”

The Postictal State: A Neglected Entity in the Management of Epilepsy

“…Neurotransmitters are available in several types of releasable pools (20). With initial electrical stimulation, there may be mobilization of such pools from calcium influx, but the releasable transmitter may be depleted with ongoing stimulation.…”