Ethanol withdrawal reduces the number of spontaneously active ventral tegmental area dopamine neurons in conscious animals

Withdrawal from chronic ethanol treatment leads to a reduction in the electrical activity in dopamine (DA) neurons in the ventral tegmental area (VTA). However, there is disagreement on how the electrical activity is reduced (i.e., in the number of spontaneously active DA neurons or their firing rates and burst firing activity) and on the underlying mechanisms. The use of general anesthesia has been suggested to cause this discrepancy. In the present study, we demonstrate that ethanol withdrawal, in conscious animals, causes a reduction in the number of spontaneously active VTA DA neurons, but not in their firing rate or burst firing activity. Similar results were obtained in a previous study using anesthetized preparation, showing that general anesthesia does not cause this difference. Ethanol withdrawal-induced reduction in a number of spontaneously active VTA DA neurons could be mediated by depolarization inactivation because this effect was reversed by systemic administration of amphetamine, which inhibits VTA DA neurons by hyperpolarization. In addition, the withdrawal effect was normalized by acute ethanol administration, suggesting that the decrease in the number of spontaneously active VTA DA neurons represents an adaptational change to chronic ethanol treatment. Because the electrical activity of DA neurons controls the release of DA, it is possible that the decreased DA release during ethanol withdrawal observed in previous studies is caused by the reduction in the electrical activity of VTA DA neurons.