Ethanol exposure decreases glutamate uptake in the nucleus accumbens

Alcohol Clin Exp Res. 2005 Mar;29(3):326-33. doi: 10.1097/01.alc.0000156086.65665.4d.


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.

MeSH terms

  • Actins / metabolism
  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Blotting, Western
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / pharmacology*
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Glutamic Acid / metabolism*
  • Male
  • Microdialysis
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Actins
  • Amino Acid Transport System X-AG
  • Central Nervous System Depressants
  • Excitatory Amino Acid Transporter 2
  • Ethanol
  • Glutamic Acid