Alcohol decreases N-methyl-D-aspartate (NMDA) receptor function since low concentrations of alcohol inhibit ion flux through NMDA receptor channels.

• NMDA antagonists substitute for alcohol in rat studies and have alcohol like effects in humans.
• There is increased release of glutamate during alcohol withdrawal in rats and increased glutamate in CSF of humans during withdrawal.
• Chronic alcohol exposure increases NMDA receptor numbers and the increase in receptor numbers relates to increased withdrawal seizures that can be reduced with NMDA antagonists.
• Individuals with a positive family history for alcohol dependence have a reduced dysphoric response to a NMDA antagonist.
• Memantine, a NMDA receptor antagonist, reduces alcohol cue induced craving in alcohol dependent subjects.
• Acamprosate, a drug that reduces NMDA receptor function reduces alcohol consumption in rats and it has shown efficacy in the treatment of alcohol dependence.