ASSESSMENT OF POTENTIAL SUBSTANCE ABUSE TREATMENT MEDICATIONS IN NONHUMAN PRIMATE MODELS. NIDA REF. NO. N01DA-19-8946; POP: 12/16/2018-12/15/2020.

摘要： 本项目的主要目标是使用两种已确立的范例确定化合物的作用：（1）药物辨别和（2）自我给药。两个不同的实验方案，预处理和替代，可以在每个范例内进行。在药物辨别范例中，将训练雄性恒河猴辨别肌内注射的可卡因和盐水。随后，将通过确定在治疗前给予的选定剂量是否降低可卡因的辨别刺激效应（预处理）和/或化合物本身的选择性剂量是否可以产生可卡因样效应（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IV导管，并接受培训，以在日常会话中自我给药IV可卡因，其中还包括食物自我给药组件。将在Mm中检测每种编码化合物，其中已确定IV可卡因自我给药的剂量-反应函数。在治疗前方案中，将进行试验，首先，确定减少IV可卡因峰值强化单位剂量自我给药而不显著改变食物自我给药的治疗前剂量，其次，确定该剂量如何改变IV自我给药的可卡因剂量反应函数。在替代方案中，将通过IV自我给药提供选定单位剂量的编码化合物，以评价其强化作用。后续研究可能会与有前途的化合物进行。

Abstract: 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.