Khanna J M, Shah G, Chau A
Department of Pharmacology, University of Toronto, Canada.
Pharmacol Biochem Behav. 1997 Aug;57(4):693-7. doi: 10.1016/s0091-3057(96)00390-5.
We have recently reported that pretreatment with NMDA receptor antagonists [(+)MK-801 and ketamine] inhibited the development of rapid tolerance to ethanol hypothermia and motor-impairment on day 2 in animals receiving ethanol on day 1, compared to the control group pretreated with saline. In these studies rats were tested at 30, 60, 90 and 120 min after ethanol on both day 1 and 2. In the present report we compared the development of rapid tolerance under 2 different conditions: (1) in groups of rats that were tested on the tilt-plane at all test times (Testing or Intoxicated Practice group), (2) in groups of rats that were not tested on the tilt-plane but were handled at all test times on day 1 (dummy testing). Rats were pretreated with ethanol or saline on day 1 and tested with ethanol on day 2 in all the above studies. Both testing (intoxicated practice) and dummy testing of animals on day 1 after pretreatment with ethanol produced rapid tolerance to ethanol on day 2. However, (+)MK-801 or ketamine pretreatment, which blocked rapid tolerance in the intoxicated practice testing paradigm, failed to block rapid tolerance in the dummy testing paradigm. Similar results were obtained for rapid tolerance and for the effect of ketamine in the hypothermia experiment. These findings suggest that NMDA antagonists block rapid tolerance in the intoxicated testing paradigm but not in the dummy testing paradigm. However, whether the two types of rapid tolerance tested in the present experiments are indeed different or interrelated remains to be further investigated.
我们最近报告称，与用生理盐水预处理的对照组相比，用NMDA受体拮抗剂[（+）MK-801和氯胺酮]预处理可抑制在第1天接受乙醇的动物在第2天对乙醇低温和运动障碍快速耐受性的发展。在这些研究中，大鼠在第1天和第2天乙醇给药后30、60、90和120分钟进行测试。在本报告中，我们比较了两种不同条件下快速耐受性的发展情况：（1）在所有测试时间在倾斜平面上进行测试的大鼠组（测试或中毒练习组），（2）在第1天所有测试时间不在倾斜平面上进行测试但进行处理的大鼠组（假测试）。在上述所有研究中，大鼠在第1天用乙醇或生理盐水预处理，并在第2天用乙醇进行测试。在第1天用乙醇预处理后对动物进行测试（中毒练习）和假测试均在第2天产生了对乙醇的快速耐受性。然而，（+）MK-801或氯胺酮预处理在中毒练习测试范式中可阻断快速耐受性，但在假测试范式中未能阻断快速耐受性。在低温实验中，快速耐受性和氯胺酮的作用也得到了类似的结果。这些发现表明，NMDA拮抗剂在中毒测试范式中可阻断快速耐受性，但在假测试范式中则不能。然而，本实验中测试的两种快速耐受性是否确实不同或相互关联仍有待进一步研究。
