Weinstock M, Dalith M, Shohami E
J Pharmacol Exp Ther. 1983 Jul;226(1):232-7.
The effect of morphine and oxotremorine, a centrally acting cholinergic agonist on the respiratory rate and arterial blood gases, was studied in rabbits given saline, increasing doses of morphine (5 mg/kg, 2 days; 10 mg/kg, 2 days; and 20 mg/kg, 3 days) injected at 12-hr intervals for 1 week. Care was taken to ensure that the chronically morphine-treated rabbits were neither under the influence of a previous dose of morphine nor in a phase of withdrawal when the response to test doses was measured. Tolerance to the respiratory depressant effect of morphine was demonstrated by the finding that a 5 times greater dose of morphine was needed to decrease respiration rate and raise arteriolar pCO2 than that given to saline-treated rabbits. The respiratory stimulant effect of oxotremorine, as demonstrated by an increase in respiration rate and decrease in PaCO2, was significantly greater in morphine-tolerant rabbits. It is concluded that chronic opiate treatment can induce supersensitivity of the cholinergic systems subserving control of respiration.
在兔子身上研究了吗啡和中枢性胆碱能激动剂氧化震颤素对呼吸频率和动脉血气的影响。给兔子每隔12小时注射一次生理盐水、递增剂量的吗啡（5毫克/千克，共2天；10毫克/千克，共2天；20毫克/千克，共3天），持续1周。在测量对测试剂量的反应时，小心确保长期接受吗啡治疗的兔子既不受前一剂吗啡的影响，也不处于戒断阶段。通过以下发现证明了对吗啡呼吸抑制作用的耐受性：与给予生理盐水治疗的兔子相比，需要5倍剂量的吗啡才能降低呼吸频率并提高小动脉pCO2。氧化震颤素的呼吸刺激作用，表现为呼吸频率增加和PaCO2降低，在吗啡耐受的兔子中显著增强。得出的结论是，慢性阿片类药物治疗可诱导参与呼吸控制的胆碱能系统超敏反应。
