Schulteis G, Markou A, Gold L H, Stinus L, Koob G F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
J Pharmacol Exp Ther. 1994 Dec;271(3):1391-8.
In addition to classic somatic signs of opiate withdrawal, a number of behavioral measures are known to be sensitive, reliable indices of naloxone-precipitated opiate withdrawal in rats. It has been suggested that some behavioral indices of withdrawal may be more sensitive to precipitation by naloxone than some somatic signs of withdrawal. The purpose of the present study was to permit a quantitative assessment of the relative sensitivity to naloxone of a variety of behavioral and somatic indices of opiate withdrawal. Male Wistar rats were implanted s.c. with either two morphine (each 75 mg of base) or two placebo pellets. No sooner than 3 days after implantation, naloxone dose-response functions were determined with several behavioral paradigms and ratings of a variety of somatic withdrawal signs. In dependent rats, very low (0.004 or 0.01 mg/kg) doses of naloxone produced the following behavioral effects: 1) a reduction in spontaneous locomotor activity, 2) a disruption of schedule-controlled (fixed ratio 15) operant responding for food, 3) an elevation in intracranial self-stimulation thresholds and 4) a conditioned place aversion. These same doses of naloxone produced no significant effects in nondependent (placebo pellet-implanted) rats. The ED50 values for naloxone precipitation of all behavioral signs of withdrawal were below 0.013 mg/kg; the ED50 values for naloxone precipitation of most somatic withdrawal signs were higher. The behavioral measures used in these studies therefore represent highly sensitive indices of opiate withdrawal.
除了阿片类药物戒断的经典躯体体征外，已知一些行为指标是大鼠中纳洛酮诱发的阿片类药物戒断的敏感、可靠指标。有人提出，某些戒断行为指标可能比某些戒断躯体体征对纳洛酮诱发更敏感。本研究的目的是对阿片类药物戒断的各种行为和躯体指标对纳洛酮的相对敏感性进行定量评估。雄性Wistar大鼠皮下植入两颗吗啡（每颗含75mg碱基）或两颗安慰剂丸。植入后不早于3天，用几种行为范式和各种躯体戒断体征的评分来确定纳洛酮剂量反应函数。在成瘾大鼠中，极低剂量（0.004或0.01mg/kg）的纳洛酮产生了以下行为效应：1）自发运动活动减少；2）食物的定时控制（固定比率15）操作性反应中断；3）颅内自我刺激阈值升高；4）条件性位置厌恶。相同剂量的纳洛酮在未成瘾（植入安慰剂丸）的大鼠中未产生显著影响。纳洛酮诱发所有戒断行为体征的ED50值均低于0.013mg/kg；纳洛酮诱发大多数躯体戒断体征的ED50值更高。因此，这些研究中使用的行为指标是阿片类药物戒断的高度敏感指标。
