Ethanol-induced excitation of ventral tegmental area dopamine (DA VTA) neurons is thought to be critical for the reinforcing effects of ethanol. Although ligand-gated ion channels are known to be the targets of ethanol, ethanol modulation of voltage-dependent ion channels of central neurons has not been well studied. We have demonstrated that ethanol excites DA VTA neurons by the reduction of sustained K⁺ current and recently reported that M-current (I_M) regulates action potential generation through fast and slow afterhyperpolarization phases. In the present study, therefore, we examined whether ethanol inhibition of I_M contributes to the excitation of rat DA VTA neurons using nystatin-perforated patch current- and voltage-clamp recordings in acutely dissociated neurons. Ethanol (20-120 mM) reduced I_M in a concentration-dependent manner and increased the spontaneous firing frequency of DA VTA neurons. The ethanol-induced increase in firing frequency correlated positively with ethanol inhibition of I_M with a slope value of 1.3. Specific I_M inhibition by XE991 (0.3-10 µM) increased firing frequency which was correlated positively with I_M inhibition with a slope value of 0.5. In the presence of 10 µM XE991, a concentration which produced maximal inhibition of I_M, ethanol still increased the firing frequency of DA VTA neurons in a concentration-dependent manner. Thus, we conclude that while ethanol causes inhibition of I_M and inhibition of I_M can result in increased firing frequency of DA VTA neurons, another effect of ethanol is primarily responsible for the ethanol-induced increase in firing rate of these neurons.