Ethanol exposure decreases glutamate uptake in the nucleus accumbens.
BACKGROUND
An increased level of extracellular glutamate is a key neurochemical feature associated with ethanol exposure and withdrawal.


METHODS
In the current study, extracellular levels of glutamate and glutamate transport in the nucleus accumbens were assayed 24 hr after repeated ethanol exposure (1 g/kg ip daily for 7 days) with use of in vivo no-net-flux microdialysis and in vitro [(3)H]glutamate uptake, respectively.


RESULTS
Microdialysis revealed higher extracellular glutamate concentrations in the nucleus accumbens of rats that were given ethanol. The increase in basal extracellular glutamate levels was accounted for in part by a decrease in the in vivo probe recovery of glutamate. Moreover, an in vitro accumbens slice preparation measuring [(3)H]glutamate uptake revealed that Na(+)-dependent [(3)H]glutamate uptake was significantly reduced 24 hr after 7 days of repeated ethanol exposure. The ethanol-induced deficit in glutamate uptake was not associated with decreased total tissue levels of the transporters GLAST or GLT1. The in vivo and in vitro ethanol-induced changes in glutamate levels and uptake returned to control levels 14 days after discontinuing 7 days of repeated ethanol exposure.


CONCLUSIONS
These results suggest that the previously reported increases in extracellular glutamate induced by ethanol exposure may be due in part to deficits in glutamate transport.
Melendez
Roberto I
RI
Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA. melendez@musc.edu
Hicks
Megan P
MP
Cagle
Stephanie S
SS
Kalivas
Peter W
PW
D000199:Actins / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D027322:Amino Acid Transport System X-AG; D002492:Central Nervous System Depressants; D027342:Excitatory Amino Acid Transporter 2; D000431:Ethanol; D018698:Glutamic Acid