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1 Prisms of adult rat cortex were maintained in vitro in either aerobic conditions (control) or conditions simulating an acute ischaemic challenge (hypoxia with no added glucose). 2 Endogenous glutamate e ux increased with time in ischaemic conditions, being 2.7 fold higher than control e ux at 45 min. Returning prisms to control solution after 20 min of simulated ischaemia resulted in glutamate e ux returning to near-control values. Endogenous GABA e ux in ischaemic conditions also increased, being 4.5 fold higher than control e ux at 45 min. 3 Ischaemia-induced glutamate e ux was not accompanied by increased lactate dehydrogenase e ux and was unaltered by omitting calcium from the extra-cellular solution and adding EGTA (0.1 mM). 4 Both GABA and the GABA-mimetic clomethiazole inhibited ischaemia-induced glutamate e ux, with IC 50 values of 26 and 24 mM respectively. The maximum inhibition by either drug was 60 ± 70%. Bicuculline (10 mM) abolished the inhibitory e ect of GABA (100 mM) but not clomethiazole (100 mM). Picrotoxin (100 mM) abolished the action of both GABA and clomethiazole. 5 Pentobarbitone inhibited glutamate e ux at 100 ± 300 mM (maximal inhibition: 39%). Bicuculline (10 mM) abolished this e ect. 6 These data suggest that ischaemia-induced glutamate e ux from rat cerebral cortex is calciumindependent and not due to cell damage up to 45 min. The inhibitory e ect of GABA, clomethiazole and pentobarbitone on ischaemia-induced glutamate e ux appears to be mediated by GABA A receptors. The results suggest that clomethiazole, unlike pentobarbitone, is able to activate the GABA A receptor-linked chloride channel directly and not merely potentiate the e ect of endogenous GABA.

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