Khanna J M, Kalant H, Shah G, Chau A
Department of Pharmacology, University of Toronto, Canada.
Brain Res Bull. 1992 Feb;28(2):311-4. doi: 10.1016/0361-9230(92)90193-2.
The motor impairment (tilt-plane test) responses to ethanol were significantly reduced on days 2, 3, 4, or 5 in rats receiving ethanol (2.3 and 1.7 g/kg) 24 and 22 h earlier, compared to the control group pretreated with saline. Administration of (+)MK-801, prior to behavioral testing with ethanol on day 1, inhibited the development of tolerance on all these days. Tolerance and the inhibitory effect of (+)MK-801 could no longer be seen if the second injection of ethanol was given on day 7, 8 or 11. Administration of (+)MK-801 on day 1 but after behavioral testing with ethanol did not block the development of rapid tolerance to ethanol on day 2. Administration of another commonly employed NMDA antagonist, i.e., ketamine, prior to ethanol on day 1, also blocked the development of rapid tolerance to ethanol. The findings suggest that NMDA antagonists block rapid tolerance by preventing some adaptation that occurs during intoxicated practice.
与用生理盐水预处理的对照组相比，在提前24小时和22小时接受乙醇（2.3克/千克和1.7克/千克）的大鼠中，乙醇引起的运动功能损害（倾斜平面试验）反应在第2、3、4或5天显著降低。在第1天用乙醇进行行为测试之前给予（+）MK-801，在所有这些日子里均抑制了耐受性的形成。如果在第7、8或11天进行第二次乙醇注射，则不再能观察到耐受性和（+）MK-801的抑制作用。在第1天进行乙醇行为测试之后给予（+）MK-801，并未阻止在第2天对乙醇快速耐受性的形成。在第1天乙醇给药之前给予另一种常用的NMDA拮抗剂即氯胺酮，也阻止了对乙醇快速耐受性的形成。这些发现表明，NMDA拮抗剂通过阻止在醉酒训练期间发生的某些适应性变化来阻断快速耐受性。
