Abdelkader Dahchour 1* and Philippe De Witte 2

1. Département de pharmacologie, Ingénierie moléculaire et biochimique, unité de Neuropsychopharmacologie, Institut National des Plantes Médicinales et Aromatiques, Université Sidi Mohamed Ben Abdellah, Fès, Morocco.
2. Laboratoire de Biologie du Comportement, Place Croix du Sud 1, Université Catholique de Louvain, B-1348, Louvain-la-Neuve, Belgium

Abstract

The effects of chronic acamprosate (400 mg/kg/day; PO) under chronic ethanol treatment on amino acids in the hippocampus of Wistar male rats were examined during the third ethanol withdrawal period. In this study, rats were made ethanol dependent by four-week vapour inhalation. After this first cycle of chronic ethanol treatment (CET), rats underwent repeated and alternate cycles of 24h withdrawals and one week of CET.
The microdialysis experiment was performed during the third ethanol withdrawal, together with the HPLC and electrochemical detection to quantify different amino acids such as aspartate, glutamate, taurine and alanine. During the first 4h of ethanol withdrawal, there were no significant changes in glutamate levels between acamprosate and non-acamprosate treated groups. During 4h and 8h 30 min glutamate levels were significantly decreased in non-acamprosate treated group by comparison to acamprosate treated group. After 10h from ethanol withdrawal glutamate levels were significantly increased in acamprosate non-treated group by comparison to acamprosate treated group. No changes were observed in other amino acids levels such as aspartate, taurine and alanine.
The results of this work suggest that by acting on glutamate receptors chronic acamprosate could prevent neuroadaptation in glutamatergic system and thereby acamprosate may provide a protective mechanism against the neurotoxicity by reducing excitatory amino acids overexpression during repeated ethanol withdrawal.

Key word : Acamprosate, Glutamate, Ethanol withdrawal, Microdialysis, Hippocampus