Ethanol reduces evoked dopamine release and slows clearance in the rat medial prefrontal cortex

Ethanol (EtOH) intoxication affects cognitive performance, contributing to attentional deficits and poor decision making, which may occur via actions in the medial prefrontal cortex (mPFC). mPFC function is modulated by the catecholamines dopamine and norepinephrine. In this study, we examine the acute effects of EtOH on electrically evoked dopamine release and clearance in the mPFC of anesthetized rats naïve to alcohol or chronically exposed to alcohol during adolescence. Methods: Dopamine release and clearance was evoked by electrical stimulation of the ventral tegmental area (VTA) and measured in the mPFC of anesthetized rats with fast-scan cyclic voltammetry. In Experiments 1 and 2, effects of a high dose of EtOH (4 g/kg, intraperitoneally) on dopamine neurotransmission in the mPFC of EtOH-naïve rats and rats given EtOH exposure during adolescence were investigated. Effects of cumulative dosing of EtOH (0.5 to 4 g/kg) on the dopamine release and clearance were investigated in Experiment 3. Experiment 4 studied effects of EtOH locally applied to the VTA on the dopamine neurotransmission in the mPFC of EtOH-naïve rats. Results: A high dose of EtOH decreased evoked dopamine release within 10 minutes of administration in EtOH-naïve rats. When tested via cumulative dosing from 0.5 to 4 g/kg, both 2 and 4 g/kg EtOH inhibited evoked dopamine release in the mPFC of EtOH-naïve rats, while 4 g/kg EtOH also slowed dopamine clearance. A similar effect on electrically evoked dopamine release in the mPFC was observed after infusion of EtOH into the VTA. Interestingly, intermittent EtOH exposure during adolescence had no effect on observed changes in mPFC dopamine release and clearance induced by acute EtOH administration. Conclusions: Taken together, these data describe EtOH-induced reductions in the dynamics of VTA-evoked mPFC dopamine release and clearance, with the VTA contributing to the attenuation of evoked mPFC dopamine release induced by EtOH.