Decades after ethanol was first described as a GABA mimetic, the precise mechanisms that produce the acute effects of ethanol and the physiological adaptations that underlie ethanol tolerance and dependence remain unclear. While a substantial body of evidence suggests that ethanol acts on GABAergic neurotransmission to enhance inhibition in the CNS, the precise mechanisms underlying the physiological effects of both acute and chronic ethanol exposure are still under investigation. We have used in vitro ethanol exposure followed by recording of miniature inhibitory postsynaptic currents (mIPSCs) to determine whether acute or chronic ethanol exposure directly alters synaptic GABAA receptor function or GABA release in cultured cortical and hippocampal neurons. Acute ethanol exposure slightly increased the duration of mIPSCs in hippocampal neurons but did not alter mIPSC kinetics in cortical neurons. Acute ethanol exposure did not change mIPSC frequency in either hippocampal or cortical neurons. One day of chronic ethanol exposure produced a transient decrease in mIPSC duration in cortical neurons but did not alter mIPSC kinetics in hippocampal neurons. Chronic ethanol exposure did not change mIPSC frequency in either hippocampal or cortical neurons. Chronic ethanol exposure also did not produce substantial cross-tolerance to a benzodiazepine in either hippocampal or cortical neurons. The results suggest that ethanol exposure in vitro has limited effects on synaptic GABAAR function and action-potential independent GABA release in cultured neurons and suggests that ethanol exposure in cultured cortical and hippocampal neurons may not reproduce all of the effects that occur in vivo and in acute brain slices
