Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment

Abstract

Background: The mesolimbic dopamine pathway, which originates in the ventral tegmental area (VTA), is important for the rewarding effects of ethanol. Acute administration of ethanol has been shown to excite dopaminergic neurons of the VTA. Chronic ethanol treatment has been reported to alter the in vitro response of dopaminergic neurons to NMDA and dopamine. The present electrophysiological study tested the hypothesis that the effect of ethanol, gamma-aminobutyric acid (GABA), and NMDA on individual dopaminergic VTA (DA-VTA) neurons from C57BL/6J mice would be changed by chronic treatment with ethanol.

Methods: C57BL/6J mice were injected intraperitoneally twice daily with either saline or ethanol in saline (3.5 g/kg) for at least 21 days. Extracellular single unit recordings of spontaneous action potentials were made from DA-VTA neurons in brain slices from these mice. Ethanol (20-120 mM), GABA (50-500 microM), or NMDA (2-20 microM) was administered in the superfusate, and the resulting change in firing rate was measured.

Results: There was no significant difference in mean basal spontaneous firing rate of DA-VTA neurons between saline-treated and ethanol-treated mice. The DA-VTA neurons from ethanol-treated mice were excited by ethanol more potently than those from saline-treated mice. Dopaminergic VTA neurons from ethanol-treated mice were inhibited less potently by GABA than those from saline-treated mice. There was no difference in the potency of NMDA to excite DA-VTA neurons from saline-treated and ethanol-treated mice.

Conclusions: Chronic treatment of C57BL/6J mice with ethanol injections sensitizes DA-VTA neurons to ethanol excitation and also decreases the inhibitory potency of GABA. The increase in sensitivity to ethanol excitation of dopaminergic VTA neurons after chronic ethanol treatment may increase the reward value of ethanol. This sensitization to ethanol activation may be an important change in reward area neurons and may contribute to the development of alcoholism.