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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics April 2001, 297 (1) 27-34;
Evgeny A. Budygin
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Paul E. M. Phillips
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Donita L. Robinson
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Andrew P. Kennedy
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Raul R. Gainetdinov
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R. Mark Wightman
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Abstract

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.

Footnotes

  • Send reprint requests to: Dr. R. M. Wightman, Department of Chemistry, Venable Hall CB #3290, University of North Carolina, Chapel Hill, NC 27599-3290. E-mail:rmw{at}unc.edu

  • This research was funded by National Institute on Drug Abuse DA10900. D.L.R. is supported from National Institute of Alcohol Abuse and Alcoholism Training Grant AA07573.

  • Abbreviations:
    SNc
    substantia nigra pars compacta
    CP
    caudate putamen
    FSCV
    fast scan cyclic voltammetry
    • Received October 2, 2000.
    • Accepted December 18, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 297 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 297, Issue 1
1 Apr 2001
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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics April 1, 2001, 297 (1) 27-34;

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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics April 1, 2001, 297 (1) 27-34;
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