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 man ipulation of DA D-2 receptors in the ventral tegmental area (VTA), sys temic administration of ethanol, and inhibition of DA uptake in the nu cleus accumbens (ACB). Perfusion of 5, 25 and 100 mu M quinpirole (a D -2 agonist), or sulpiride (a D-2 antagonist) through the microdialysis probe in the VTA produced dose-related decreases or increases, respec tively, in the extracellular levels of DA in both the VTA and ACE of a dult Wistar rats. The IP administration of 2-3 g/kg ethanol produced a sustained increase in the extracellular levels of DA (150-200% of bas eline) in the ACE for at least 2 h after injection, whereas only a tra nsient increase was observed in the VTA. Local perfusion of the ACE wi th 100 mu M GBR12909, a DA uptake inhibitor, elevated the extracellula r levels of DA in the ACE to approximately 400% of baseline, but decre ased the extracellular levels of DA in the VTA to approximately 50% of baseline. Overall, the results suggest that (a) there is an associati on between somatodendritic and terminal field DA release when D-2 cell body autoreceptors in the VTA are manipulated, (b) elevating synaptic levels of DA in the terminal field activates a long-loop negative fee dback system to the VTA, and (c) different mechanisms may be mediating the actions of ethanol on DA neuronal activity and terminal DA releas e.