Ethanol dependence has limited effects on GABA or glutamate transporters in rat brain.
BACKGROUND
Neuroadaptations of GABAergic and glutamatergic systems appear to play an important role in both the acute as well as chronic effects of ethanol. Chronic ethanol intake leads to the development of ethanol tolerance and dependence that is associated with a decrease in GABAergic and an increase in glutamatergic function. The present report assessed the involvement of GABA and glutamate transporters in the chronic ethanol-induced adaptations of these two neuronal systems.


METHODS
Male and female rats were made ethanol dependent by 2-week administration of ethanol in a liquid diet. Levels of GABA (GAT-1, GAT-3) and glutamate (GLT-1, EAAC-1) transporters were assayed by immunoblotting. Transporter function was assessed by [3H]GABA and [3H]glutamate uptake assays.


RESULTS
Ethanol dependence did not alter levels of GABA or glutamate transporters in cerebral cortex compared with pair-fed control values. There were increases in some, but not all, transporter levels in hippocampus and hypothalamus with the development of ethanol dependence. A decreased rate of uptake was observed for GABA in cerebral cortex. There was no change in maximal GABA uptake or in glutamate uptake (Vmax).


CONCLUSIONS
These results suggest that alterations in GABA and glutamate transporters have only a limited role in neuroadaptations to chronic ethanol intake in rats. However, the observed alterations were region-specific, supporting the complex responses to chronic ethanol exposure and suggesting that neuroadaptations of GABAergic and glutamatergic systems vary across the brain.
Devaud
L L
LL
Department of Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Pocatello, Idaho 83209-8334, USA. ldevaud@otc.isu.edu
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D050485:GABA Plasma Membrane Transport Proteins; D050491:Glutamate Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C493415:Slc6a1 protein, rat; D027981:Symporters; D000431:Ethanol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid