SY02VENTRAL TEGMENTAL AREA DOPAMINE NEURONS AND ETHANOL: THE PUZZLE TO DISENTANGLESY02-1HETEROGENEITY OF ETHANOL RESPONSES IN THE VENTRAL TEGMENTAL AREA

Although it is know that ethanol can modify the activity of dopamine (DA) neurons located in the ventral tegmental area (VTA), how ethanol exerts this action remains unclear. Recent behavioural studies from our laboratory, supported by electrophysiological findings, suggest that ethanol, when administered directly into the VTA, is able to exert opposed effects on the activity of DA neurons. It has been proposed that two parallel and opposed mechanisms of control are involved in these responses, one promoting and the other reducing the GABA release onto VTA DA neurons. Our data suggest that the activating effects are mediated by salsolinol (a metabolite of ethanol resulting from the condensation of acetaldehyde and DA) acting on the μ-opioid receptors (MORs) located in VTA GABA neurons. On the other hand, the inhibitory effects would be triggered by the non-metabolized fraction of ethanol acting on GABAA-receptors and provoking the inhibition of VTA DA neurons. Both actions are concurrent after intra-VTA administration of ethanol, being the behavioural consequences dependent on the ethanol dose. The heterogeneity of the midbrain DA neuronal population is an additional factor that could further complicate the above mentioned scenario. Our electrophysiological studies have suggested the existence of different DA neuron sub-populations within the VTA showing different sensitivities to ethanol. DA neurons located in the medial VTA, showed a concentration-dependent increase in firing-frequency after ethanol application, whereas DA neurons located in the lateral VTA were either unresponsive or respond only to high ethanol concentrations.