Tsai G, Coyle J T
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Boston, USA.
Annu Rev Med. 1998;49:173-84. doi: 10.1146/annurev.med.49.1.173.
Recent evidence suggests that ethanol abuse produces its diverse effects on the brain to a substantial degree by disrupting the function of the major excitatory neurotransmitter, glutamate. Ethanol, at concentrations associated with behavioral effects in humans, inhibits the N-methyl-D-aspartate (NMDA) receptor, which mediates the post-synaptic excitatory effects of glutamate. Tolerance to ethanol results in up-regulation of the NMDA receptor so that abrupt withdrawal produces a hyperexcitable state that leads to seizures, delerium tremens, and excitotoxic neuronal death. Ethanol's inhibition of the NMDA receptor in the fetal brain likely contributes to the CNS manifestations of fetal alcohol syndrome. Therapeutic strategies aimed at correcting glutamatergic dysregulation in alcoholism need to be explored.
最近的证据表明，乙醇滥用在很大程度上通过破坏主要兴奋性神经递质谷氨酸的功能，对大脑产生多种影响。与人类行为效应相关浓度的乙醇会抑制N-甲基-D-天冬氨酸（NMDA）受体，该受体介导谷氨酸的突触后兴奋作用。对乙醇的耐受性会导致NMDA受体上调，因此突然戒断会产生过度兴奋状态，进而导致癫痫发作、震颤谵妄和兴奋性毒性神经元死亡。乙醇对胎儿大脑中NMDA受体的抑制作用可能导致胎儿酒精综合征的中枢神经系统表现。需要探索旨在纠正酒精中毒中谷氨酸能失调的治疗策略。
