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

这个项目的主要目标是确定化合物的影响，使用两个公认的范例：(1)药物歧视和(2)自我给药。两种不同的实验方案，预处理和替代，可以在每个范例中进行。在药物识别范式中，雄性恒河猴将被训练以区分肌肉注射可卡因和生理盐水。随后，将通过确定在会前使用的选定剂量是否会减少可卡因的鉴别刺激作用（预处理）和/或选定剂量的化合物本身是否会产生类似可卡因的作用（替代）来研究编码化合物。在药物自我给药范例中，Mm将准备留置静脉导管，并在日常会议中接受自我静脉注射可卡因的培训，其中也包括食物自我给药部分。每个编码的化合物将在Mm中进行测试，其中IV可卡因自我给药的剂量-反应函数已经确定。在预处理方案中，将进行试验，首先确定一个预处理剂量，该剂量可以减少静脉注射可卡因的峰值强化单位剂量的自我给药，而不会大大改变食物的自我给药，其次，确定该剂量如何改变静脉注射自我给药的可卡因剂量反应函数。在替代方案中，选定的单位剂量的编码化合物将提供静脉自我给药，以评估其强化作用。可能会对有前景的化合物进行后续研究。

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.