Dopaminergic Neurons in the Ventral Tegmental Area of C57BL/6J and DBA/2J Mice Differ in Sensitivity to Ethanol Excitation

Abstract

The mesolimbic dopamine pathway that originates in the ventral tegmental area (VTA) is important for the rewarding effects of ethanol. Ethanol has been shown to excite dopaminergic neurons of the VTA, both in vivo and in vitro, in rats. Behavioral differences in the rewarding effects of ethanol have been observed between C57BL/6J and DBA/2J mice. The present electrophysiological study examined the effect of ethanol on individual dopaminergic VTA neurons from these two inbred mouse strains. Extracellular single unit recordings of spontaneous action potentials were made from dopaminergic VTA neurons in brain slices from either C57BL/6J or DBA/2J mice. Ethanol (10 to 160 mM) was administered in the superfusate and the mean change in firing rate produced by ethanol was measured. There was no significant difference in basal spontaneous firing rate of dopaminergic VTA neurons between these two mouse strains. Ethanol caused a concentration-dependent increase in the firing rate of neurons from both mouse strains. Ethanol excited dopaminergic VTA neurons from DBA/2J mice more potently than those from C57BL/6J mice. The difference in sensitivity to ethanol excitation of dopaminergic VTA neurons in C57BL/6J and DBA/2J mice may contribute to differences in their behavioral response to ethanol. The fact that a given concentration of ethanol causes greater excitation of dopaminergic VTA (reward) neurons in DBA/2J mice than in C57BL/6J mice could explain why DBA/2J mice show much stronger place preference conditioning with ethanol. The higher voluntary intake of ethanol by C57BL/6J mice may be partly due to the insensitivity of their dopaminergic VTA neurons that requires them to drink a lot of ethanol to achieve sufficient excitation of reward neurons, whereas DBA/2J mice avoid oral ingestion of ethanol, despite its rewarding effect, because of their aversion to its taste.