Ethanol differentially modulates GABAA receptor-mediated chloride currents in hippocampal,cortical, and septal neurons in rat brain slices

Previous electrophysiological studies have reported conflicting results concerning the effects of ethanol on γ-aminobutyric acid-A (GABA_A) receptor-mediated responses in the brain. To examine the variables that might explain these inconsistencies, the present study was designed to determine whether ethanol modulation of synaptically evoked GABA responses is brain region dependent, to identify factors that might regulate ethanol sensitivity, and to investigate the mechanism(s) underlying ethanol modulation of GABA responses. Whole-cell voltage clamp methods were used to examine the effects of ethanol on synaptically evoked GABA_A inhibitory postsynaptic currents (IPSCs) recorded from neurons in hippocampus, cerebral cortex, and intermediate lateral and medial 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 (DNQX). Superfused ethanol (80 mM) potentiated evoked GABA_A IPSCs in cortical neurons and in intermediate lateral and medial septal neurons but not in CA1 hippocampal neurons. However, the mechanism by which ethanol enhanced GABA_A IPSC amplitudes differed between brain regions. In cortex, ethanol induced a hyperpolarizing shift in the GABA_A IPSC reversal potential (E_IPSC) without modifying the underlying GABA_A receptor-mediated conductance (G_IPSC). In contrast, ethanol enhanced GABA_A IPSC amplitudes in lateral and medial septal neurons by increasing the G_IPSC without modifying the E_IPSC These results suggest that ethanol differentially modulates responses to endogenous GABA released during synaptic activation and that important differences between various brain regions may reflect multiple mechanisms of ethanol action. © 1994 Wiley-Liss, Inc.