Ventral tegmental area deep brain stimulation reverses ethanol-induced dopamine increase in the rat nucleus accumbens

The neurophysiology of alcohol use disorder (AUD) is complex, but a major contributor to addictive phenotypes is the tendency for drugs of abuse to increase tonic extracellular dopamine (DA) levels in the nucleus accumbens (NAc). Repeated exposure to substances of abuse such as ethanol results in the overstimulation of the mesolimbic pathway, causing an excessive release of DA from the ventral tegmental area (VTA) to target regions such as the NAc. This heightened DA signaling is associated with the reinforcing effects of substances, leading to a strong desire for continued use. Recent work has postulated that high frequency deep brain stimulation (DBS) of the ventral tegmental area may reduce dopamine transmission to the nucleus accumbens following acute drug of abuse exposure, thereby mitigating the drug's addictive potential. We first demonstrate ethanol's ability to decrease phasic DA release over time and to increase tonic extracellular DA concentrations in the nucleus accumbens. Next, we demonstrate the capability for high frequency VTA DBS to reverse this ethanol-associated surge in tonic DA concentrations in the nucleus accumbens to levels not significantly different from baseline. This study suggests a promising new avenue for investigating the mechanisms of alcohol use disorder.