Supported by the Fonds de la Recherche Scientifique et Médicale (1997-2002) and l'Institut de Recherches Economiques sur les Boissons (IREB) and sponsored by LIPHA-Santé.
Effects of Acamprosate on Excitatory Amino Acids During Multiple Ethanol Withdrawal Periods
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 27, Issue 3, pages 465–470, March 2003
How to Cite
Dahchour, A. and De Witte, P. (2003), Effects of Acamprosate on Excitatory Amino Acids During Multiple Ethanol Withdrawal Periods. Alcoholism: Clinical and Experimental Research, 27: 465–470. doi: 10.1097/01.ALC.0000056617.68874.18
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication August 6, 2002; accepted December 19, 2002.
- Repeated Ethanol Withdrawal;
- Excitatory Amino Acids;
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.
Conclusion: 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.