Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, Mail Code 7764, San Antonio, TX 78229, USA.
Psychopharmacology (Berl). 2010 Mar;209(1):85-94. doi: 10.1007/s00213-009-1773-3. Epub 2010 Feb 3.
Stimuli that are paired with opioid withdrawal can themselves produce effects similar to withdrawal that might promote relapse.
This study compared precipitated and conditioned withdrawal and tested whether withdrawal is modified by clonidine or morphine.
Morphine-treated rats (10 mg/kg/12 h) received naloxone (3.2 mg/kg) in a novel environment (conditioned stimuli [CS]). Other rats received naloxone in the absence of the CS. Body weight and observable signs were used to measure withdrawal.
Naloxone produced weight loss and withdrawal signs in morphine-treated rats. Following pairings of the CS and naloxone, the CS alone had effects similar to naloxone; conditioned withdrawal was greater after three naloxone/CS pairings, as compared to one, and with longer morphine treatment. Antagonist-precipitated withdrawal was greater in rats that previously were physically dependent on morphine, as compared to withdrawal in rats that were never dependent; however, conditioned withdrawal did not differ between groups. When administered concurrently with naloxone, clonidine (0.1 mg/kg) attenuated some precipitated withdrawal signs, although conditioned withdrawal was largely unchanged. Administration of 10 mg/kg of morphine before the CS alone attenuated all conditioned withdrawal signs, whereas 0.1 mg/kg of clonidine before the CS alone reduced some directly observable signs and not weight loss.
Conditioned withdrawal occurs rapidly and is greater with longer periods of morphine treatment or more pairings of naloxone and the CS; however, a history of physical dependence does not increase conditioned withdrawal. Modification of conditioned withdrawal by drugs might be a useful approach for treating relapse.
与阿片类药物戒断相关的刺激本身可能产生类似于戒断的效果，从而促进复发。
本研究比较了诱发和条件性戒断，并测试了可乐定或吗啡是否会改变戒断。
接受吗啡治疗的大鼠（10mg/kg/12h）在新环境中接受纳洛酮（3.2mg/kg）（条件刺激[CS]）。其他大鼠在没有 CS 的情况下接受纳洛酮。体重和可观察到的症状用于衡量戒断。
纳洛酮在接受吗啡治疗的大鼠中引起体重减轻和戒断症状。在 CS 和纳洛酮配对后，CS 本身具有类似于纳洛酮的效果；与一次相比，三次纳洛酮/CS 配对后，条件性戒断更为严重，且吗啡治疗时间更长。与从未依赖的大鼠相比，以前对吗啡有生理依赖性的大鼠，拮抗剂诱发的戒断更为严重；然而，条件性戒断在两组之间没有差异。当与纳洛酮同时给药时，可乐定（0.1mg/kg）减轻了一些诱发的戒断症状，尽管条件性戒断基本不变。CS 单独给予 10mg/kg 的吗啡之前，所有条件性戒断症状都减轻，而 CS 单独给予 0.1mg/kg 的可乐定则减轻一些直接观察到的症状，而不减轻体重。
条件性戒断迅速发生，并且在较长时间的吗啡治疗或纳洛酮和 CS 的更多配对后更为严重；然而，生理依赖的历史并不会增加条件性戒断。药物对条件性戒断的修饰可能是治疗复发的一种有用方法。
