IGF::OT::IGF ASSESSMENT OF POTENTIAL SUBSTANCE ABUSE TREATMENT MEDICATIONS IN NONHUMAN PRIMATE MODELS. NIDA REF. NO. N01DA-19-8946; POP: 12/16/2018-12/15/2019. PURPOSE: TO EXERCISE OPTION QUANTITIES 1

IGF::OT::IGF 对非人类灵长类动物模型中潜在药物滥用治疗药物的评估。

• 批准号: 10551131
• 负责人: JACK BERGMAN
• 金额: $ 116.15万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-16 至 2022-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551131
• 关键词: Catheters; Cocaine; Code; Dose; Exercise; Follow-Up Studies; Food; Intramuscular Injections; Macaca mulatta; Modeling; National Institute of Drug Abuse; Pharmaceutical Preparations; Protocols documentation; Saline; Self Administration; Stimulus; Testing; Training; cocaine self-administration; drug discrimination; male; nonhuman primate; response; substance abuse treatment

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.

该项目的主要目的是使用两个公认的范式来确定化合物的影响：（1）药物歧视和（2）自我管理。在每个范式中可以进行两个不同的实验方案，即预处理和替代。在药物歧视范式中，将对雄性恒河猴进行训练，以区分可卡因的肌内注射与盐水。随后，将通过确定选定的剂量，施用前的剂量，减少可卡因（预处理）和/或该化合物本身是否会产生类似可卡因的效果（替代）来研究编码化合物。在药物自我管理范式中，MM将通过留置IV导管准备，并在每日会议中接受培训以自我管理IV可卡因，其中还包括食物自我给药组件。每个编码化合物将在MM中进行测试，其中已确定了静脉内可卡因自我给药的剂量反应函数。在预处理方案中，首先将进行测试，以识别预处理剂量，以减少静脉内可卡因的峰值增强单位剂量的自给剂，而不会大大改变食物自我给药，其次，以确定可可剂量剂量响应的剂量响应对IV自我自我施加的功能如何改变。在替代方案中，将提供所选的编码化合物的单位剂量，以评估其增强作用。可以使用有希望的化合物进行后续研究。