Figure 1.

N-methyl-d-aspartate receptor (NMDAR)-mediated excitotoxic cell death. During alcohol withdrawal, it is postulated that overactivity of the NMDAR leads to excitotoxic cell death in the developing brain. A) Alcohol directly interacts with the NMDA receptor, which is activated by glutamate. Acute alcohol exposure inhibits the receptor, which contributes to the sedative and intoxicating effects of alcohol. B) Continued alcohol exposure may produce an adaptive neurocompensatory response, either as an increase in the number of NMDARs or an increase in the amount of glutamate released, which contributes to acute tolerance to alcohol’s intoxicating effects. However, when alcohol is eliminated from the body during periods of withdrawal, there may be rebound overactivity of NMDARs (C), which may lead to cell death (D).