Ethanol modulation of GABAergic inhibition in midbrain dopamine neurons: Implications for the development of alcohol-seeking behaviors

Abstract

Activation of dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. However, studies from our lab demonstrate that acute ethanol enhances GABA release onto VTA-DA neurons via activation of a G protein-coupled receptor, 5-HT2C, and subsequent activation of an intracellular calcium signaling pathway. Utilizing electrophysiological methods, in this chapter we present evidence which attempts to resolve the paradoxical nature of the dual excitatory and inhibitory actions of ethanol on DA neurons. Our results suggest that ethanol-excitation of VTA-DA neurons is bi-phasic and involves interplay of excitatory and inhibitory mechanisms which can fine tune the overall action of ethanol on DA neuron excitability. Overall, these results may provide insight into mechanisms underlying the development of alcohol dependence.