Fig. 1.

Numerous effects of ethanol have been demonstrated on VTA neurons. Acute ethanol increases the mixed Na⁺/K⁺ h-current (HCN) and also increases a barium-sensitive current (BSC). Acute ethanol also decreases m-current (I_M) and a leak potassium channel (K_leak) that contributes to increased excitability. Acute ethanol also decreases D₂ dopamine receptor desensitization (which would have the effect of increasing dopamine inhibition), possibly by reducing the activity of protein kinase C or other elements of the desensitization pathways (PKC and others). In addition to the direct actions of ethanol on the membrane of VTA neurons, there can also be significant influences of afferents to the VTA, some of which are increased (glutamate and acetylcholine) and some of which are reduced (GABA, glycine). The sum of these effects results in the ethanol-induced excitation and increased release of dopamine to target areas; chronic alcohol exposure can result in differential tolerance to one or more of these effects, altering the tonic activity of VTA neurons (Diana et al. 1992b; Shen and Chiodo 1993) and increasing the rewarding value of ethanol (Brodie 2002; Hopf et al. 2007; Rodd et al. 2005)