Ethanol depresses neurons in the lateral parabrachial nucleus by potentiating pre- and postsynaptic GABAA receptors.

As a psychoactive substance, ethanol is widely used in people's life. However, the neuronal mechanisms underlying its sedative effect remain unclear. In this study, we investigated the effects of ethanol on the lateral parabrachial nucleus (LPB), which is a novel component related to sedation. Coronal brain slices (280 μm thick) containing the LPB were prepared from C57BL/6J mice. The spontaneous firing and membrane potential of LPB neurons, and GABAergic transmission onto these neurons were recorded using whole-cell patch-clamp recordings. Drugs were applied through superfusion. The LPB neurons exhibited a regular spontaneous discharge at a rate of 1.5-3 Hz without burst firing. Brief superfusion of ethanol (30, 60, and 120 mM) concentration-dependently and reversibly suppressed the spontaneous firing of the neurons in LPB. In addition, when synaptic transmission was blocked by tetrodotoxin (TTX) (1 μM), ethanol (120 mM) caused hyperpolarization of the membrane potential. Furthermore, superfusion of ethanol markedly increased the frequency and amplitude of spontaneous and miniature inhibitory postsynaptic currents, which were abolished in the presence of the GABAA receptor (GABAA-R) antagonist picrotoxin (100 μM). In addition, the inhibitory effect of ethanol on the firing rate of LPB neurons was completely abolished by picrotoxin. Ethanol inhibits the excitability of LPB neurons in mouse slices, possibly via potentiating GABAergic transmission onto the neurons at pre- and postsynaptic sites.