ORAL METHADONE SELF-ADMINISTRATION

最近的研究结果表明，口服美沙酮可以作为 一种恒河猴的排泄器。 有一些重要的相似之处， 美沙酮维持治疗患者，因为药物是口服的， 作为一个代理人。 在美沙酮的实验室研究中 维持病人，提供少量美沙酮维持 在固定的比率下，以远高于 同时可用的车辆。 这些发现与那些 口服美沙酮的猴子作为 - 好的 如果给猴子一个简单的选择， 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 来证明这种药物的药效 跨届会 将增加量的美沙酮加入到2%乙醇溶液中， 达到0.4mg/ml的浓度。 随后，在 乙醇浓度逐渐降低到零： 美沙酮饮用持续存在，猴子消耗的量要大得多 比同时可用的水媒介物的药物溶液。 此外，药物和载体液体的位置各自颠倒 一天，猴子一直“跟踪”药物溶液。 的 拟议的研究将检查一些变量， 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， 竞争性拮抗剂和拮抗剂效应。相对强化 将确定不同药物剂量的影响， 其中一些变量将被研究。 这些研究将使 口服阿片类药物强化行为的初步表征， 非人灵长类动物，结果将提供一个经验基础 为将来的研究。 一个结果将是长期稳定的实验室 准备，这将是有用的研究，有一个基本的 科学或临床基础。 特别是这种准备将是有益的 在药物开发方面。 将有可能长期开展 改变阿片类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.