White David A, Hwang M Lisa, Holtzman Stephen G
Emory University School of Medicine, Department of Pharmacology, O.W. Rollins Research Building, 1510 Clifton Road, NE Suite 5074, Atlanta, GA 30322, USA.
Pharmacol Biochem Behav. 2005 Jul;81(3):451-8. doi: 10.1016/j.pbb.2005.04.002.
Limited preclinical research has been conducted investigating the motivational or "affective" properties of withdrawal from acute opioid dependence following a single morphine exposure. Therefore, the purpose of the present study was to pharmacologically characterize the motivational properties associated with naltrexone-precipitated withdrawal after a single injection of morphine using place conditioning. Conditioned place aversion was assessed using a biased two-compartment apparatus and procedure. Adult male Sprague-Dawley rats were given 15 min free access to the entire apparatus on day one to determine initial preferences. Beginning on the second day, combinations of either saline or morphine (1.0-10 mg/kg, s.c.) followed by naltrexone (0.003-3.0 mg/kg, s.c.) 3.75 h later were administered. Rats were then immediately confined to one compartment for 30 min. The next day, rats received the alternative treatment and were confined to the opposite compartment. Twenty-four hours later animals were tested again for 15 min while they had access to the entire apparatus. Morphine followed by naltrexone conditioned significant place aversion (CPA) with just one pairing. This effect was a function of the naltrexone and morphine doses. CPA was also dependent on morphine pretreatment time, with significant aversion only occurring 4 h after morphine pretreatment. Finally continuous morphine administration followed by a single injection of naltrexone resulted in CPA. These data extend the range of behavioral effects associated with antagonist-precipitated withdrawal from acutely administered morphine and suggest that place conditioning is an effective model in assessing motivational aspects of withdrawal from acute opioid dependence in rats.
针对单次吗啡暴露后急性阿片类药物依赖戒断的动机性或“情感”特性，所开展的临床前研究有限。因此，本研究的目的是利用条件性位置偏爱实验，从药理学角度表征单次注射吗啡后纳曲酮诱发戒断相关的动机性特性。使用有偏倚的双隔室装置和程序评估条件性位置厌恶。在第一天，给予成年雄性Sprague-Dawley大鼠15分钟自由进入整个装置的机会，以确定初始偏好。从第二天开始，给予生理盐水或吗啡（1.0 - 10毫克/千克，皮下注射），3.75小时后给予纳曲酮（0.003 - 3.0毫克/千克，皮下注射）。然后立即将大鼠限制在一个隔室中30分钟。第二天，大鼠接受另一种处理，并被限制在相对的隔室中。24小时后，再次让动物在可进入整个装置的情况下进行15分钟测试。吗啡后接纳曲酮仅经过一次配对就诱发了显著的条件性位置厌恶（CPA）。这种效应是纳曲酮和吗啡剂量的函数。CPA也依赖于吗啡预处理时间，仅在吗啡预处理4小时后才出现显著厌恶。最后，持续给予吗啡后单次注射纳曲酮导致了CPA。这些数据扩展了与急性给予吗啡后拮抗剂诱发戒断相关的行为效应范围，并表明条件性位置偏爱实验是评估大鼠急性阿片类药物依赖戒断动机方面的有效模型。
