Khanna J M, Morato G S, Kalant H
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Pharmacol Biochem Behav. 2002 May;72(1-2):291-8. doi: 10.1016/s0091-3057(01)00773-0.
The effect of N-methyl-D-aspartate (NMDA) antagonists [dizocilpine, (+)MK-801, and ketamine], an NMDA agonist (D-cycloserine) and of brain serotonin (5-HT) depletion with p-chlorophenylalanine (p-CPA) on acute tolerance to ethanol was examined, using the tolerance model proposed by Radlow [Psychopharmacology 114 (1994) 1-8] and Martin and Moss [Alcohol Clin Exp Res 17 (1993) 211-216]. This model is based on the concept of a linear increase of acute tolerance with time; the rate of acute tolerance development is the slope of the output function that relates blood alcohol concentrations (BACs) and intoxication. Pretreatment with NMDA antagonists inhibited the development of acute tolerance to ethanol, whereas pretreatment with D-cycloserine enhanced it. Depletion of 5-HT by p-CPA also blocked acute tolerance to ethanol. These results on acute tolerance are similar to those previously found on rapid and chronic tolerance to ethanol.
使用Radlow [《精神药理学》114 (1994) 1 - 8]以及Martin和Moss [《酒精临床与实验研究》17 (1993) 211 - 216]提出的耐受模型，研究了N - 甲基 - D - 天冬氨酸（NMDA）拮抗剂[地佐环平、(+)MK - 801和氯胺酮]、一种NMDA激动剂（D - 环丝氨酸）以及用对氯苯丙氨酸（p - CPA）使脑5 - 羟色胺（5 - HT）耗竭对乙醇急性耐受的影响。该模型基于急性耐受随时间呈线性增加的概念；急性耐受发展速率是将血液酒精浓度（BACs）与中毒联系起来的输出函数的斜率。用NMDA拮抗剂预处理可抑制对乙醇急性耐受的发展，而用D - 环丝氨酸预处理则增强了这种耐受。p - CPA使5 - HT耗竭也阻断了对乙醇的急性耐受。这些关于急性耐受的结果与先前在对乙醇的快速和慢性耐受中发现的结果相似。
