Vol. 297, Issue 1, 27-34, April 2001

Effect of Acute Ethanol on Striatal Dopamine Neurotransmission in Ambulatory Rats

Evgeny A. Budygin, Paul E. M. Phillips, Donita L. Robinson, Andrew P. Kennedy, Raul R. Gainetdinov and R. Mark Wightman

Department of Chemistry and Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina (E.A.B., P.E.M.P., D.L.R., A.P.K., R.M.W.); and Department of Cell Biology, Duke University, Durham, North Carolina (R.R.G.)

The effect of ethanol on evoked dopamine release in the caudate putamen has been measured in behaving animals with in vivo electrochemistry. Dopamine was measured with fast-scan cyclic voltammetry in adult male rats to resolve the competing processes of dopamine uptake and release. Ethanol dose dependently decreased dopamine efflux compared with saline-treated animals: to 89% of controls with 0.5 g/kg, 70% with 1 g/kg, 34% with 2.5 g/kg, and 18% with 5 g/kg. This decrease was not due to a change in uptake, as measured by the rate of dopamine disappearance after stimulation, and therefore can be attributed to decreased dopamine release. Additionally, it was not mediated by a decrease in biosynthesis, as measured by L-DOPA accumulation after NSD 1015 administration. The selective dopamine uptake inhibitor GBR 12909 compensated for the effects of high doses of ethanol on dopamine release. Moreover, GBR 12909 induced faster restoration of the righting reflex in rats sedated with 2.5 g/kg, but not 5 g/kg, ethanol. In brain slices containing the caudate putamen, ethanol suppressed dopamine release only at the highest dose tested (200 mM). The difference in responses between the slice and the intact animal indicates that ethanol exerts its effects in the cell body regions of dopamine neurons as well as in terminals. These neurochemical results, combined with published accounts of microdialysis measures of extracellular dopamine and electrophysiological recordings of dopamine neurons, demonstrate that ethanol has a profound effect on dopamine neurons whose net result is a suppression of dopamine neurotransmission at high doses.