Pierce T L, Raper C
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Australia.
J Pharmacol Toxicol Methods. 1995 Nov;34(3):149-55. doi: 10.1016/1056-8719(95)00060-8.
Previous studies of opiate dependence in our laboratory have shown that opiate-naive (control) animals can display behaviors normally ascribed to withdrawal following naloxone challenge. The possibility arises that in these control rats, the stress of the induction of dependence, pharmacological challenge, and behavioral testing may result in the release of endogenous opioids such that on naloxone administration withdrawal behaviors are elicited. In the present study, we have utilized two differing experimental protocols for the induction of morphine dependence in rats that would represent the extremes of normal laboratory handling procedures and have then assessed withdrawal behaviors following naloxone challenge. In control animals, the results show that the stressors alone are insufficient to allow for the precipitation of naloxone-induced withdrawal. However, withdrawal behavior was generally greater in the opiate-dependent animals in the "high" rather than the "low" stress group, suggesting a summation of opiate effects. Similarly, a residual effect was noted in the control opiate-naive animals; naloxone rather than saline (control) challenged rats displayed a slightly higher incidence of withdrawal behavior. These results stress the importance of maintaining constant laboratory protocols, minimizing stressful procedures, and performing appropriate controls in assessing opiate dependence and withdrawal.
我们实验室之前对阿片类药物依赖的研究表明，初次接触阿片类药物（对照）的动物在纳洛酮激发后可表现出通常归因于戒断的行为。在这些对照大鼠中，可能出现的情况是，诱导依赖的应激、药理学激发和行为测试可能导致内源性阿片类物质释放，从而在给予纳洛酮时引发戒断行为。在本研究中，我们采用了两种不同的实验方案来诱导大鼠吗啡依赖，这两种方案代表了正常实验室操作程序的两个极端情况，然后评估了纳洛酮激发后的戒断行为。在对照动物中，结果表明仅应激源不足以引发纳洛酮诱导的戒断。然而，“高”应激组而非“低”应激组的阿片类药物依赖动物的戒断行为通常更明显，这表明存在阿片类药物效应的累加。同样，在初次接触阿片类药物的对照动物中也观察到了残留效应；纳洛酮而非生理盐水（对照）激发的大鼠表现出戒断行为的发生率略高。这些结果强调了在评估阿片类药物依赖和戒断时保持恒定的实验室方案、尽量减少应激程序以及进行适当对照的重要性。
