ETHANOL DIFFERENTIALLY MODULATES GABA(A) RECEPTOR-MEDIATED CHLORIDE CURRENTS IN HIPPOCAMPAL, CORTICAL, AND SEPTAL NEURONS IN RAT-BRAIN SLICES

Previous electrophysiological studies have reported conflicting result s concerning the effects of ethanol on gamma-aminobutyric acid-A (GABA (A)) receptor-mediated responses in the brain. To examine the variable s that might explain these inconsistencies, the present study was desi gned to determine whether ethanol modulation of synaptically evoked GA BA responses is brain region dependent, to identify factors that might regulate ethanol sensitivity, and to investigate the mechanism(s) und erlying ethanol modulation of GABA responses. Whole-cell voltage clamp methods were used to examine the effects of ethanol on synaptically e voked GABA(A) inhibitory postsynaptic currents (IPSCs) recorded from n eurons in hippocampus, cerebral cortex, and intermediate lateral and m edial septum from rat brain slice preparations. Bicuculline-sensitive IPSCs elicited by local stimulation were pharmacologically isolated by pretreatment with the glutamate specific antagonists, DL-(-)-2-amino- 5-phosphonovaleric acid (APV) and 6,7-dinitroquinoxaline-2,3-dione (DN QX). Superfused ethanol (80 mM) potentiated evoked GABA(A) inhibitory postsynaptic currents IPSCs in cortical neurons and in intermediate la teral and medial septal neurons but not in CA1 hippocampal neurons. Ho wever, the mechanism by which ethanol enhanced GABA(A) IPSC amplitudes differed between brain regions. In cortex, ethanol induced a hyperpol arizing shift in the GABA(A) IPSC reversal potential (E(IPSC)) without modifying the underlying GABA(A) receptor-mediated conductance (G(IPS C)) In Contrast, ethanol enhanced GABA(A) IPSC amplitudes in lateral a nd medial septal neurons by increasing the G(IPSC) without modifying t he E(IPSC). These results suggest that ethanol differentially modulate s responses to endogenous GABA released during synaptic activation and that important differences between various brain regions may reflect multiple mechanisms of ethanol action. (C) 1994 Wiley-Liss, Inc.