FY14. BASE AWARD; ASSESSMENT OF POTENTIAL COCAINE TREATMENT MEDICATIONS IN NON-HUMAN PRIMATES; POP 12/16/2013-12/15/2014; N01DA-14-8913

该项目的主要目标是使用两个公认的范例来确定化合物的效果：(1)药物歧视和(2)自我给药。在每个范例中，可以进行两种不同的实验方案，即前处理和替代。在药物辨别模式中，雄性恒河猴将接受训练，以区分肌肉注射可卡因和生理盐水。随后，将通过确定会前给予的选定剂量是否减少可卡因的辨别性刺激效应(预处理)和/或选定剂量的化合物本身是否可产生类似可卡因的效果(替代)来研究编码化合物。在药物自我给药模式中，MM将准备留置静脉导管，并在包括食物自我给药成分的日常会议中接受自我给药静脉注射可卡因的培训。每种编码化合物都将在mm中进行测试，在mm中已经确定了静脉注射可卡因自身给药的剂量反应函数。在预处理方案中，将进行测试，第一，确定减少静脉注射可卡因的最大强化单位剂量的自我给药而不会显著改变食物自我给药的预处理剂量，第二，确定该剂量如何改变静脉注射可卡因的剂量反应函数。在替代方案中，编码化合物的选定单位剂量将通过静脉自给药获得，以评估其增强效果。后续研究可能会用有前景的化合物来进行。

The main objectives of this project are to determine the effects of compounds using two well-established paradigms: (1) drug discrimination and (2) self-administration. Two distinct experimental protocols, pretreatment and substitution, may be conducted within each paradigm. In the drug discrimination paradigm, male rhesus monkeys will be trained to discriminate an intramuscular injection of cocaine from saline. Subsequently, coded compounds will be studied by determining whether selected doses, administered pre-session, reduce the discriminative-stimulus effects of cocaine (pretreatment) and/or whether selective doses of the compound itself can produce cocaine-like effects (substitution). In the drug self-administration paradigm, Mm will be prepared with indwelling IV catheters, and trained to self-administer IV cocain in daily sessions that also include food self-administration components. Each coded compound will be tested in Mm in which the dose-response function for IV cocaine self-administration has been determined. In the pretreatment protocol, tests will be conducted, first, to identify a pretreatment dose that reduces self-administration of the peak reinforcing unit dose of IV cocaine without greatly altering food self-administration, and second, to determine how that dose alters the cocaine dose response function for IV self-administration. In the substitution protocol, selected unit doses of the coded compound will be made available of IV self-administration to evaluate their reinforcing effects. Follow-up studies may be conducted with promising compounds.