Young A M, Sannerud C A, Steigerwald E S, Doty M D, Lipinski W J, Tetrick L E
Department of Psychology, Wayne State University, Detroit, MI 48202.
Psychopharmacology (Berl). 1990;102(1):59-67. doi: 10.1007/BF02245745.
Experiments assessed the development of tolerance to morphine stimulus control during treatment with selected maintenance doses of morphine. Separate groups of rats were trained to discriminate saline and either 3.2 mg/kg or 5.6 mg/kg morphine under fixed-ratio schedules of food delivery. Dose-response functions for generalization of morphine stimulus control were determined before, during, and after repeated treatment with selected doses of morphine. Similar experiments were performed with repeated pentobarbital treatment in order to assess the pharmacological selectivity of tolerance. Repeated treatment with saline, 3.2 mg/kg morphine, or twice daily injections of 17.8 mg/kg pentobarbital produced no tolerance to morphine stimulus control. In contrast, treatment with daily injections of 10 mg/kg or twice daily injections of 10 or 17.8 mg/kg morphine produced a dose-dependent increase in the dose of morphine required for stimulus control. The magnitude of tolerance to morphine stimulus control varied directly with the maintenance dose of morphine and was slightly greater for a lower than a higher morphine training dose. Termination of repeated treatment was followed by a return to initial sensitivity, without additional training. Tolerance to morphine stimulus control was not necessarily accompanied by tolerance to its rate-suppressing effects.
实验评估了在使用选定维持剂量的吗啡进行治疗期间，对吗啡刺激控制耐受性的发展情况。将不同组的大鼠训练为在固定比率的食物递送模式下区分生理盐水和3.2毫克/千克或5.6毫克/千克的吗啡。在使用选定剂量的吗啡进行重复治疗之前、期间和之后，确定吗啡刺激控制泛化的剂量反应函数。为了评估耐受性的药理学选择性，对戊巴比妥进行了重复治疗并开展了类似实验。用生理盐水、3.2毫克/千克吗啡或每日两次注射17.8毫克/千克戊巴比妥进行重复治疗，未产生对吗啡刺激控制的耐受性。相比之下，每日注射10毫克/千克吗啡或每日两次注射10或17.8毫克/千克吗啡进行治疗，会使刺激控制所需的吗啡剂量呈剂量依赖性增加。对吗啡刺激控制的耐受性程度与吗啡的维持剂量直接相关，且较低吗啡训练剂量时的耐受性略高于较高吗啡训练剂量。重复治疗终止后，无需额外训练即可恢复到初始敏感性。对吗啡刺激控制的耐受性不一定伴随着对其速率抑制作用的耐受性。
