Effects of Ethanol on GABAA Receptors in GABAergic and Glutamatergic Presynaptic Nerve Terminals

Ethanol (EtOH) has a number of behavioral effects, including intoxication, amnesia, and/or sedation, that are thought to re-late to the activation of GABAA receptors. However, GABAA receptors at different cellular locations have different sensitivi-ties to EtOH. The present study used the “synaptic bouton” preparation where we could stimulate nerve endings on me-chanically dissociated single rat hippocampal CA1 and CA3 pyramidal neurons and investigate the effects of EtOH on pre-synaptic and postsynaptic GABAA receptors. Low concentra-tions of EtOH (10 mM) had no effect on postsynaptic GABAA and glutamate receptors or voltage-dependent Na and Ca2 channels. Higher concentrations (100 mM) could significantly inhibit these current responses. EtOH at 10 mM had no direct effect on inhibitory postsynaptic currents (IPSCs) and excit-atory postsynaptic currents (EPSCs) evoked by focal stimula-tion of single boutons [evoked IPSCs (eIPSCs) and evoked EPSCs (eEPSCs)]. However, coapplication of 10 mM EtOH with muscimol decreased the amplitude of eIPSCs and eEPSCs and increased their paired-pulse ratio. The effects on eEPSCs were reversed by bicuculline. Coapplication of muscimol and EtOH significantly increased the frequency of spontaneous IPSCs and EPSCs. The EtOH effects on the postsynaptic responses and eEPSCs were similar in neurons from neonatal and mature rats. These results revealed that low concentrations of EtOH can potentiate the activation of presynaptic GABAA receptors to inhibit evoked GABA and glutamate release. These results indicate a high sensitivity of presynaptic GABAA receptor to EtOH, which needs to be accounted for when considering the cellular mechanisms of EtOH’s physiological responses