Wilson W R, Bosy T Z, Ruth J A
School of Pharmacy, University of Colorado, Boulder 80309.
Alcohol. 1990 Sep-Oct;7(5):389-95. doi: 10.1016/0741-8329(90)90021-4.
Involvement of glutamate neurotransmission in the differential response of long-sleep (LS) and short-sleep (SS) mice to acute ethanol was examined by measuring the effect of centrally administered glutamate receptor agonists and antagonists on blood ethanol concentration (BEC) at loss of righting response following intragastric administration of ethanol. NMDA coinjected with glycine, and quinolinic acid (QA), decreased sensitivity to ethanol in both lines of mice. SS mice were more sensitive to QA than were LS. The NMDA antagonists 2-amino-5-phosphonovaleric acid (APV), MK-801 and an inhibitor of glutamate synthesis, methionine sulfoximine, increased sensitivity to ethanol in both lines of mice. MK-801 effects were line dependent with SS being more sensitive. In addition, coinjection of APV, Mg++ or Zn++ with QA blocked the decrease in sensitivity seen with QA alone. These results demonstrate that NMDA agonists and antagonists alter the acute hypnotic response to ethanol in both LS and SS mice, and support the hypothesis that ethanol exerts its effects in part by altering glutamatergic neurotransmission.
通过测量胃内给予乙醇后翻正反射消失时，中枢给予谷氨酸受体激动剂和拮抗剂对血液乙醇浓度（BEC）的影响，研究了谷氨酸神经传递在长睡眠（LS）和短睡眠（SS）小鼠对急性乙醇的差异反应中的作用。与甘氨酸共同注射的NMDA和喹啉酸（QA）降低了两种品系小鼠对乙醇的敏感性。SS小鼠比LS小鼠对QA更敏感。NMDA拮抗剂2-氨基-5-磷酸戊酸（APV）、MK-801以及谷氨酸合成抑制剂甲硫氨酸亚砜亚胺增加了两种品系小鼠对乙醇的敏感性。MK-801的作用存在品系依赖性，SS小鼠更敏感。此外，APV、Mg++或Zn++与QA共同注射可阻断单独使用QA时观察到的敏感性降低。这些结果表明，NMDA激动剂和拮抗剂改变了LS和SS小鼠对乙醇的急性催眠反应，并支持乙醇部分通过改变谷氨酸能神经传递发挥作用的假说。
