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.

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 benzodiazepine Ro 5-4864 (60 mg/kg) produced convulsions in mice that could be antagonised either by diazepam (2-4 mg/kg) or by Ro 15-1788 (10-20 mg/kg). In mice and rats subconvulsant doses of Ro 5-4864 were proconvulsant when combined with subconvulsant doses of picrotoxin or pentylenetetrazole. Ro 15-1788 antagonised the tonic convulsions triggered by the drug combinations when it was given at the same time as Ro 5-4864; this antagonism was not observed when the drugs were injected at different times. In contrast to a previous report, we could find no evidence that Ro 5-4864 antagonised seizures induced by electroshock. Using two different ligand-binding techniques, no evidence was seen for the existence in rat brain of the previously reported "micromolar" benzodiazepine receptor, a suggested site of action of Ro 5-4864.

1 The release of endogenous y-aminobutyric acid (GABA) from slices of rat cortex, hippocampus and striatum prepared both 30 min and 24 h after the last of a series of electroconvulsive shocks (5 seizures given spread out over 10 days) has been investigated. 2 No change in spontaneous (basal) release was observed. However, 30 min after the last convulsion, K+-evoked GABA release above basal release was inhibited in both hippocampus (20%) and striatum (33%) but not in the cortex. Release was still inhibited in striatum (22%) 24 h after the last seizure. 3 In confirmation of an earlier report, chronic electroconvulsive shock was found to increase basal GABA content in striatum and inhibit synthesis by 34%. The synthesis rate was also inhibited in the hippocampus (44%) but not in the cortex. 4 Glutamic acid decarboxylase activity was unchanged in all regions after repeated electroconvulsive shock treatment. 5 It is proposed that repeated electroconvulsive shocks lead to a substantial inhibition of release in the striatum and hippocampus and a long-term inhibition of GABA synthesis in these regions. Such changes may be associated with the altered monoamine biochemistry and function observed after repeated electroconvulsive shock and with the mechanism of the antidepressant action of electroconvulsive therapy.

1 A method is described ofmeasuring the K+-evoked release ofendogenous 5-hydroxytryptamine (5-HT) and noradrenaline (NA) from slices prepared from rat cortex. 2 There was no difference in either the spontaneous (basal) or K+-evoked release of 5-HT or NA from cortical slices prepared from handled animals and those given a single electroconvulsive shock (ECS) either 30 min or 24 h earlier.3 In chronic studies, rats were either handled or given an ECS 5 times over 10 days and cortical slices prepared. There was no difference in 5-HT or NA release between the groups 30 min after the last treatment other than a modest attentuation of spontaneous NA release following ECS treatment. However 24 h after the last treatment K+-evoked release (above basal release) of 5-HT and NA was inhibited by 84% and 48%, respectively. 4 These data demonstrate that following a single ECS, normal 5-HT and NA release is seen at a time when GABA release is markedly inhibited. After repeated ECS the release of both monoamines was markedly inhibited. These 5-HT changes may be involved in the enhanced 5-HT-receptor function seen after repeated ECS.