The effects of ethanol on dopaminergic neurons of the ventral tegmental area studied with intracellular recording in brain slices.

Dopaminergic neurons in the ventral tegmental area of Tsai (VTA) have been implicated in the mediation of the rewarding effects of ethanol and many other drugs of abuse. Our previous extracellular studies in brain slices have demonstrated that ethanol increases the firing rate of dopaminergic neurons in the VTA. In the present intracellular study, ethanol (40-160 mM) increased the spontaneous firing rate of most (77%) VTA neurons. In addition, most (75%) VTA neurons were depolarized by ethanol. Ethanol also changed the shape of the spontaneous action potential in VTA neurons, reducing the amplitude of the spike after-hyperpolarization (in 74% of neurons) and also reducing the amplitude of the depolarizing phase of the action potential (in 86% of neurons tested). Furthermore, analysis of Voltage/Current curves in the presence and absence of ethanol showed that ethanol had little effect on the resistance of the cell membrane at membrane potentials near rest, but enhanced the time-dependent inward rectification activated at more hyperpolarized membrane potentials (Ih). This intracellular study identifies several electrophysiological effects of ethanol that may underlie the ethanol-induced excitation of VTA neurons and, therefore, may be important for the rewarding effects of ethanol.