Mucha R F, van der Kooy D, O'Shaughnessy M, Bucenieks P
Brain Res. 1982 Jul 8;243(1):91-105. doi: 10.1016/0006-8993(82)91123-4.
Rats display a preference for an environment in which they previously received morphine. The present report provides behavioral and pharmacological data for this simple model of reinforcement produced by opiates and describes an aversion in rats for an environment in which they previously received naloxone. Preferences were produced with intravenous (i.v.) morphine sulfate at doses of 0.08-15 mg/kg and durations of the pairing between environment and morphine of 10 min to 1.5 h. Preferences were also seen with other opiate agonists (etorphine-HCl and levorphanol-tartrate), another route of drug administration (subcutaneous), and after 1-4 administrations of morphine. Cocaine-HCl (i.v.), a non-narcotic drug, known to be self-administered by humans, also produced a place preference. Lithium chloride (i.v.), an agent found to be a punishing stimulus in other situations, produced a place aversion. There was no appreciable preference for an environment paired with dextrorphan-tartrate and naloxone-HCl (2 mg/kg, i.p.) blocked the production of the preference produced by i.v. morphine. In contrast to the effect produced by morphine, aversions were produced with (-)-naloxone-HCl alone at doses of 0.1-45 mg/kg (i.v.). The aversion was not produced at (+)-naloxone. Implantation of rats with a 75 mg morphine pellet 3 days prior to place conditioning potentiated the aversive effect of naloxone. It was concluded that place conditioning produced by morphine and naloxone is mediated by specific opiate receptors and that stimulating and decreasing activity of the endogenous opioid peptide system with systemically administered drugs is positively reinforcing and aversive, respectively. The discussion emphasizes application of the simple and sensitive place conditioning model to drug reinforcement research, including analyses of reinforcement produced by microinjection of opiates into the brain.
大鼠对其先前接受过吗啡的环境表现出偏好。本报告提供了关于阿片类药物产生的这种简单强化模型的行为和药理学数据，并描述了大鼠对其先前接受过纳洛酮的环境的厌恶。偏好是通过静脉注射（i.v.）剂量为0.08 - 15 mg/kg的硫酸吗啡产生的，环境与吗啡之间的配对持续时间为10分钟至1.5小时。在使用其他阿片类激动剂（盐酸埃托啡和酒石酸左啡诺）、另一种给药途径（皮下注射）以及吗啡给药1 - 4次后也观察到了偏好。盐酸可卡因（i.v.），一种已知人类会自行服用的非麻醉药物，也产生了位置偏好。氯化锂（i.v.），一种在其他情况下被发现是惩罚性刺激的药物，产生了位置厌恶。与酒石酸右啡烷配对的环境没有明显偏好，并且腹腔注射（i.p.）2 mg/kg的盐酸纳洛酮可阻断静脉注射吗啡产生的偏好。与吗啡产生的效应相反，单独使用剂量为0.1 - 45 mg/kg（i.v.）的（-）-盐酸纳洛酮会产生厌恶。（+）-纳洛酮不会产生厌恶。在进行位置条件反射前3天给大鼠植入75 mg吗啡丸增强了纳洛酮的厌恶效应。得出的结论是，吗啡和纳洛酮产生的位置条件反射是由特定的阿片受体介导的，并且通过全身给药刺激和降低内源性阿片肽系统的活性分别具有正强化作用和厌恶作用。讨论强调了这种简单且敏感的位置条件反射模型在药物强化研究中的应用，包括对将阿片类药物微量注射到大脑中产生的强化作用的分析。
