Acute ethanol decreases dopamine transporter velocity in rat striatum: in vivo and in vitro electrochemical measurements.
BACKGROUND
Ethanol increases dopamine transporter (DAT) velocity when measured in cell expression systems, but its effects in vivo are mixed. The present experiments examined the effect of acute ethanol on dopamine transmission, particularly DAT velocity, in anesthetized animals as well as rat striatal suspensions.


METHODS
To determine the effect of acute ethanol on DAT function in vivo, we measured dopamine uptake in real time using fast-scan cyclic voltammetry and constant potential amperometry in the olfactory tubercle of anesthetized rats. Dopamine fibers were electrically stimulated, and the resulting transient dopamine signals were analyzed to describe the release and uptake kinetics. We also measured the effect of ethanol on DAT velocity in vitro in striatal tissue suspensions using rotating disk electrode voltammetry.


RESULTS
Ethanol (2.5 and 4 g/kg, intraperitoneally) decreased the electrically stimulated dopamine signal in the olfactory tubercle by 35-55%. The slope of the clearance curve of dopamine was 40% shallower after both doses of ethanol, indicating slower uptake. Modeling the data using Michaelis-Menten uptake kinetics showed that the slower uptake was due to a decrease in DAT V(max). These results were confirmed in vitro, because ethanol decreased the velocity of dopamine uptake by 35% in striatal tissue suspensions.


CONCLUSIONS
These results indicate that acute ethanol decreases DAT function in rat dorsal and ventral striatum in anesthetized rats and tissue suspensions, in contrast to its effects on human DAT expressed in single cells. Given the variety of molecular targets of ethanol in the brain, including the DAT itself, it is likely that several mechanisms converge to produce a net effect on DAT regulation and function that could very well be different in intact tissue versus single cells.
Robinson
Donita L
DL
Department of Chemistry, Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
Volz
Trent J
TJ
Schenk
James O
JO
Wightman
R Mark
RM
D000465:Algorithms; D000818:Animals; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004563:Electrochemistry; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009830:Olfactory Bulb / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493216:Slc6a3 protein, rat; D000431:Ethanol; D004298:Dopamine