Abstract
The effects of various benzodiazepine receptor ligands on the GABA autoreceptor have been studied in slices of cerebral cortex of the rat. The GABA a receptor agonist muscimol inhibited the K +-stimulated release of [ 3H]GABA with a pIC 25 of 7.65 ± 0.11. This effect was antagonised by the GABA a receptor antagonist bicuculline, which had an IC 50, of 0.36 ± 0.03 μ M. Small concentrations (< 1 μM) of the benzodiazepine full agonist clonazepam did not significantly alter K +-evoked release of [ 3H]GABA but shifted the concentration-effect curve for muscimol to the left. This effect was blocked by the benzodiazepine antagonist flumazenil. By contrast, the benzodiazepine full inverse agonist methyl β-carboline-3-carboxylate shifted the muscimol concentration-effect curve to the right and this too was blocked by flumazenil. The results suggest that the GABA autoreceptor in cortical slices from the rat is modulated by a benzodiazepine receptor.
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