Heishman S J, Schuh K J, Schuster C R, Henningfield J E, Goldberg S R
Clinical Pharmacology and Therapeutics Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Psychopharmacology (Berl). 2000 Feb;148(3):272-80. doi: 10.1007/s002130050051.
Although most opioid self-administration research has been conducted with laboratory animals, such research with humans is necessary to answer questions unique to human drug-taking behavior.
We investigated the influence of morphine dose and an alternative non-drug reinforcer on choice between morphine versus money and examined the relationship between drug-reinforced behavior and subjective euphoria.
Five male opioid users participated in the 7-week study. During the first 5 weeks, a single dose of morphine (0, 4, 8, 16, or 32 mg/70 kg) was available each week. On Monday, subjects received an IM injection of the dose tested that week. On Tuesday, Thursday, and Friday, subjects could work for morphine or money under a second-order, progressive ratio schedule. For each primary ratio completed on the drug lever, subjects earned one-ninth of the available drug dose, and for each ratio completed on the money lever, subjects earned $1. Total amount of drug earned was administered in a single IM injection at the end of the session; money earned was credited to the subject's account.
As morphine dose increased, responding for drug increased in an orderly manner and responding for money decreased. During the final phase of the study, the lowest and highest doses that maintained drug responding for each subject were repeated, and the value of the alternative reinforcer was increased to $2 per ratio. This manipulation was associated with decreased drug-maintained responding at the lowest, but not the highest, reinforcing dose of morphine.
The progressive ratio, concurrent access procedure may be useful in predicting the outcome of drug abuse treatment interventions that use alternate reinforcement strategies.
尽管大多数阿片类药物自我给药研究是在实验动物身上进行的，但对人类进行此类研究对于回答人类药物使用行为特有的问题是必要的。
我们研究了吗啡剂量和一种替代性非药物强化物对吗啡与金钱选择的影响，并考察了药物强化行为与主观欣快感之间的关系。
五名男性阿片类药物使用者参与了这项为期7周的研究。在前5周，每周提供一剂吗啡（0、4、8、16或32毫克/70千克）。周一，受试者接受当周测试剂量的肌肉注射。周二、周四和周五，受试者可以在二阶累进比率程序下为获得吗啡或金钱而工作。在药物操作杆上完成每个初级比率，受试者可获得可用药物剂量的九分之一，在金钱操作杆上完成每个比率，受试者可获得1美元。在实验结束时，将获得的药物总量以单次肌肉注射的方式给药；获得的金钱记入受试者账户。
随着吗啡剂量增加，对药物的反应呈有序增加，对金钱的反应减少。在研究的最后阶段，重复每个受试者维持药物反应的最低和最高剂量，并将替代性强化物的价值提高到每个比率2美元。这种操作与最低强化剂量（而非最高强化剂量）的吗啡维持的药物反应减少有关。
累进比率、并行获取程序可能有助于预测使用替代强化策略的药物滥用治疗干预的结果。
