TY - JOUR T1 - Ethanol Antagonizes Kainate Receptor-Mediated Inhibition of Evoked GABA<sub>A</sub> Inhibitory Postsynaptic Currents in the Rat Hippocampal CA1 Region JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 937 LP - 944 DO - 10.1124/jpet.102.038471 VL - 303 IS - 3 AU - T. L. Crowder AU - O. J. Ariwodola AU - J. L. Weiner Y1 - 2002/12/01 UR - http://jpet.aspetjournals.org/content/303/3/937.abstract N2 - Many studies have demonstrated that ethanol reduces glutamatergic synaptic transmission primarily by inhibiting theN-methyl-d-aspartate subtype of glutamate receptor. In contrast, the other two subtypes of ionotropic glutamate receptor (α-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 GABAA inhibitory postsynaptic currents (IPSCs) in the rat hippocampal CA1 pyramidal cell region. Under our recording conditions, bath application of 1 μM kainate significantly inhibited GABAA IPSCs. This inhibition seemed to be mediated by the activation of somatodendritic kainate receptors on GABAergic interneurons and the subsequent activation of metabotropic GABAB receptors, because the kainate inhibition was largely blocked by pretreating slices with a GABAB receptor antagonist. Ethanol pretreatment significantly antagonized the inhibitory effect of kainate on GABAA IPSCs, at concentrations as low as 20 mM. In contrast, ethanol did not block the direct inhibitory effect of a GABAB receptor agonist on GABAA 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. ER -