ORAL METHADONE SELF-ADMINISTRATION

最近的研究结果表明，口服美沙酮可以作为 恒河猴的增强剂。有一些重要的相似之处 美沙酮维持性患者口服药物并 起到增强剂的作用。在美沙酮的实验室研究中 维持性患者，少量美沙酮维持 在固定比率下的响应速度远远高于 可同时使用的车辆。这些发现与那些 用猴子获得的口服美沙酮作为 增强剂。如果给猴子一个简单的选择，喝一杯 美沙酮溶液或水，他们会避免美沙酮溶液。 因此，培训程序是必要的。可以使用衰落过程 以确定药物是一种增强剂。跨会话块 将越来越多的美沙酮加入2%的乙醇溶液中，直到 浓度可达0.4 mg/ml。随后，跨 会议期间，乙醇浓度逐渐降至零： 美沙酮的饮用量持续存在，猴子的消费量要大得多 比同时可用的水载器的药物溶液的更多。 此外，药物和车用液体的位置各颠倒 一天，猴子们一直在“跟踪”药物溶液。这个 拟议的研究将检查一些变量，这些变量 控制药物强化行为的重要性。其中包括药物 剂量，时间表大小，食物限制，滥用药物组合， 相互竞争的增强剂和对抗性效应。相对强化 将确定不同药物剂量的影响，并相互作用 其中一些变量将被研究。这些研究将允许 口服阿片类药物强化行为的初步表征 非人灵长类，这一结果将提供经验基础 以备将来研究之用。一个结果将是一个长期稳定的实验室 在基础研究中将有用的准备工作 科学基础或临床基础。特别是，这一准备工作将是有用的 在药物开发方面。将有可能进行长期的 对改变阿片类药物强化行为的药物的连续研究。

Recent findings demonstrate that orally delivered methadone can serve as a reinforcer for rhesus monkeys. There are important parallels with methadone maintenance patients in that the drug is taken orally and functions as a reinforcer. In laboratory studies with methadone maintenance patients, delivery of small volumes of methadone maintains responding under fixed-ratios and at much higher rates than the concurrently available vehicle. These findings are the same as those obtained with monkeys for who orally delivered methadone serves as a reinforcer. If monkeys are simply given the option of drinking a methadone solution or water, they will avoid the methadone solution. Thus a training procedure is necessary. A fading procedure can be used to establish the drug as a reinforcer. Across blocks of sessions increasing amounts of methadone are added to a 2% ethanol solution until a concentration of 0.4 mg/ml is reached. Subsequently, across blocks of sessions the ethanol concentration is gradually decreased to zero: Methadone drinking persists, and the monkeys consume much larger volumes of the drug solution than of the concurrently available water vehicle. Moreover, the positions of the drug and vehicle liquids are reversed each day, and the monkeys consistently "track" the drug solution. The proposed research will examine a number of variables that are of importance in controlling drug reinforced behavior. These include drug dose, schedule size, food restriction, abused drug combinations, competing reinforcers, and antagonist effects. The relative reinforcing effects of different drug doses will be determined, and interactions among some of the variables will be studied. These studies will permit an initial characterization of oral opioid reinforced behavior in a nonhuman primate, and the results will provide an empirical foundation for future studies. One outcome will be a chronic stable laboratory preparation that will be useful in studies that have either a basic science or clinical basis. In particular this preparation will be useful in medication development. It will be possible to carry out long-term sequential studies of drugs that alter opioid reinforced behavior.