Grant K A, Valverius P, Hudspith M, Tabakoff B
Unit for Special Projects, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Eur J Pharmacol. 1990 Feb 13;176(3):289-96. doi: 10.1016/0014-2999(90)90022-x.
Prior biochemical and electrophysiological studies have shown that low doses of ethanol inhibited calcium influx through the N-methyl-D-aspartate (NMDA) receptor/ionophore. The present data show that chronic ethanol treatment results in an increase in the number of NMDA receptor/ionophore complexes in the hippocampus, a brain area known to be associated with ethanol withdrawal seizure activity. Treatment during withdrawal with NMDA-exacerbated handling induced withdrawal seizures in the ethanol-dependent mice, while administration of the NMDA receptor-associated calcium channel antagonist MK-801 decreased the occurrence and severity of the withdrawal seizures in a dose-dependent manner. The results are consistent with the hypothesis that the up-regulation of the NMDA receptor systems following chronic ethanol treatment may mediate the seizures associated with ethanol withdrawal in dependent animals.
先前的生化和电生理研究表明，低剂量乙醇可抑制通过N-甲基-D-天冬氨酸（NMDA）受体/离子载体的钙内流。目前的数据表明，慢性乙醇处理导致海马体中NMDA受体/离子载体复合物数量增加，海马体是已知与乙醇戒断癫痫活动相关的脑区。在戒断期间用NMDA加剧处理会诱发乙醇依赖小鼠的戒断癫痫，而给予与NMDA受体相关的钙通道拮抗剂MK-801则以剂量依赖的方式降低了戒断癫痫的发生率和严重程度。这些结果与以下假设一致，即慢性乙醇处理后NMDA受体系统的上调可能介导了依赖动物中与乙醇戒断相关的癫痫发作。
