['Acamprosate reduces relapse, and the drug may interact with glutamate transmission and with glutamate/NMDA receptors. Because these systems are implicated in excess calcium entry leading to alcohol withdrawal-induced neurotoxicity, we evaluated the effects of acamprosate on these parameters in neuronal cultures.', 'Primary cultures of neocortical neurons from fetal Sprague-Dawley rats were maintained either in normal medium or in medium containing 100 mM ethanol for 4 days. After this time, cultures were challenged with glutamate for 10 min and then returned to medium (all in the absence of ethanol). 45Ca2+ uptake was measured during the challenge, and glutamate-induced toxicity was assessed after 20 hr. The effects of acamprosate present during the glutamate challenge were measured on both parameters.', 'In controls, acamprosate did not significantly affect glutamate-induced neurotoxicity but produced a significant inhibition of calcium entry. The NMDA receptor antagonists dizocilpine and d-amino-phosphonovalerate (D-APV) inhibited both glutamate neurotoxicity and calcium entry. In cultures previously exposed to ethanol, glutamate-induced neurotoxicity and calcium entry were both significantly enhanced. Dizocilpine reduced both these parameters to unstimulated control values, and D-APV reduced both calcium entry and neurotoxicity with the same relation that we obtained in control cultures. In the ethanol-withdrawn cultures, acamprosate reduced both the enhanced glutamate-induced calcium entry and the enhanced neurotoxicity in a concentration-dependent manner. Acamprosate also significantly reduced calcium entry caused by 80 mM K+ in control and ethanol-exposed cultures.'] Is acamprosate neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain?