Berkowitz B A, Finck A D, Hynes M D, Ngai S H
Anesthesiology. 1979 Oct;51(4):309-12. doi: 10.1097/00000542-197910000-00006.
The purpose of these experiments was to characterize the nature of tolerance to the analgesic action of nitrous oxide. Analgesia was assessed in rats using a tail-flick latency test and in mice using an abdominal constriction test. Rats and mice were exposed to nitrous oxide, 75 per cent, the balance oxygen, continuously for 16--18 hours. On re-exposure to nitrous oxide 30 min later, these animals were found tolerant to nitrous oxide in that the analgesic response was decreased by at least 50 per cent. Animals tolerant to nitrous oxide were not tolerant to morphine. Morphine (0.25--1.5 mg/kg) produced equal degrees of analgesia in control and nitrous oxide-tolerant mice and rats. In contrast, rats made tolerant to morphine by repeated daily injections of as much as 400 mg/kg subcutaneously or by subcutaneous implantation of morphine pellets (75 mg, twice) showed a decreased analgesic response to nitrous oxide. Thus the cross-tolerance between nitrous oxide and morphine appears unique in that it is unidirectional.
这些实验的目的是确定对一氧化二氮镇痛作用产生耐受性的本质。使用甩尾潜伏期试验在大鼠中评估镇痛效果，使用腹部收缩试验在小鼠中评估镇痛效果。大鼠和小鼠持续暴露于75%的一氧化二氮和其余为氧气的混合气体中16至18小时。30分钟后再次暴露于一氧化二氮时，发现这些动物对一氧化二氮产生了耐受性，因为镇痛反应至少降低了50%。对一氧化二氮产生耐受性的动物对吗啡没有耐受性。吗啡（0.25至1.5毫克/千克）在对照小鼠和大鼠以及对一氧化二氮产生耐受性的小鼠和大鼠中产生同等程度的镇痛效果。相比之下，通过每天皮下重复注射高达400毫克/千克或皮下植入吗啡丸剂（75毫克，两次）而对吗啡产生耐受性的大鼠，对一氧化二氮的镇痛反应降低。因此，一氧化二氮和吗啡之间的交叉耐受性似乎很独特，因为它是单向的。
