Effects of acamprosate on excitatory amino acids during multiple ethanol withdrawal periods.
BACKGROUND
Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals.


METHODS
In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high-performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate.


RESULTS
An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels.


CONCLUSIONS
The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate.
Dahchour
Abdelkader
A
Université catholique de Louvain-Biologie du Comportement, 1, Place Croix du Sud, B-1348 Louvain-la-Neuve, Belgium. dahchour@bani.ucl.ac.be
De Witte
Philippe
P
D000077443:Acamprosate; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology*
D018846:Excitatory Amino Acids; D013654:Taurine; D000431:Ethanol; D000077443:Acamprosate