Ethanol antagonizes kainate receptor-mediated inhibition of evoked GABA(A) inhibitory postsynaptic currents in the rat hippocampal CA1 region

Abstract

Many studies have demonstrated that ethanol reduces glutamatergic synaptic transmission primarily by inhibiting the N-methyl-D-aspartate subtype of glutamate receptor. In contrast, the other two subtypes of ionotropic glutamate receptor (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate) have generally been shown to be insensitive to intoxicating concentrations of ethanol. However, we have previously identified a population of kainate receptors that mediate slow excitatory postsynaptic currents in the rat hippocampal CA3 pyramidal cell region that is potently inhibited by low concentrations of ethanol. In this study, we examined the effect of ethanol on kainate receptor-mediated inhibition of evoked GABA(A) inhibitory postsynaptic currents (IPSCs) in the rat hippocampal CA1 pyramidal cell region. Under our recording conditions, bath application of 1 microM kainate significantly inhibited GABA(A) IPSCs. This inhibition seemed to be mediated by the activation of somatodendritic kainate receptors on GABAergic interneurons and the subsequent activation of metabotropic GABA(B) receptors, because the kainate inhibition was largely blocked by pretreating slices with a GABA(B) receptor antagonist. Ethanol pretreatment significantly antagonized the inhibitory effect of kainate on GABA(A) IPSCs, at concentrations as low as 20 mM. In contrast, ethanol did not block the direct inhibitory effect of a GABA(B) receptor agonist on GABA(A) IPSCs. The results of this study suggest that modest concentrations of ethanol may antagonize presynaptic, as well as postsynaptic, kainate receptor function in the rat hippocampus.