Ethanol and negative feedback regulation of mesolimbic dopamine release in rats

The objectives of this study were to examine the relationship between somatodendritic and terminal field dopamine (DA) release following manipulation of DA D2 receptors in the ventral tegmental area (VTA), systemic administration of ethanol, and inhibition of DA uptake in the nucleus accumbens (ACB). Perfusion of 5, 25 and 100 microM quinpirole (a D2 agonist), or sulpiride (a D2 antagonist) through the microdialysis probe in the VTA produced dose-related decreases or increases, respectively, in the extracellular levels of DA in both the VTA and ACB of adult Wistar rats. The IP administration of 2-3 g/kg ethanol produced a sustained increase in the extracellular levels of DA (150-200% of baseline) in the ACB for at least 2 h after injection, whereas only a transient increase was observed in the VTA. Local perfusion of the ACB with 100 microM GBR12909, a DA uptake inhibitor, elevated the extracellular levels of DA in the ACB to approximately 400% of baseline, but decreased the extracellular levels of DA in the VTA to approximately 50% of baseline. Overall, the results suggest that (a) there is an association between somatodendritic and terminal field DA release when D2 cell body autoreceptors in the VTA are manipulated, (b) elevating synaptic levels of DA in the terminal field activates a long-loop negative feedback system to the VTA, and (c) different mechanisms may be mediating the actions of ethanol on DA neuronal activity and terminal DA release.