Pharmacology of Stimulant Choice

兴奋剂选择的药理学

• 批准号: 10585535
• 负责人: Matthew L Banks
• 金额: $ 34.93万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585535
• 关键词: Acceleration; Admission activity; Agonist; Animals; Attenuated; Basic Science; Behavior; Behavioral; Biological Assay; Biosensor; CHRM1 gene; Cessation of life; Cholinergic Agonists; Clinical; Clinical Data; Clinical Trials; Cocaine; Cocaine Abuse; Cocaine use disorder; Data; Decision Making; Development; Dopamine; Dose; Drug Addiction; Drug Use Disorder; Effectiveness; Experimental Designs; Failure; Female; Food; Funding; Human; Laboratory Animals; Laboratory Study; Measures; Mediator; Methamphetamine; Methamphetamine use disorder; Microdialysis; Modeling; Monitor; Muscarinic Acetylcholine Receptor; Muscarinics; National Institute of Drug Abuse; Negative Reinforcements; Neurobiology; Neurotransmitters; Nucleus Accumbens; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Prefrontal Cortex; Procedures; Public Health; Publications; Rattus; Research; Research Subjects; Self Administration; Series; Serotonin Agonists; Signal Transduction; Source; Stimulant; System; Testing; Time; United States Food and Drug Administration; United States National Institutes of Health; Work; antagonist; effectiveness evaluation; experimental study; human subject; in vivo; male; methamphetamine abuse; non-drug; overdose death; pharmacologic; pre-clinical; reinforcer; social; stimulant abuse; stimulant misuse; stimulant use disorder; therapeutic candidate

This new R01 application proposes a systematic series of experiments focused on drug-choice procedures in male and female rats to evaluate the muscarinic acetylcholine receptor (mAChR)1 agonist VU0364572 as a candidate medication for treatment of cocaine and methamphetamine use disorder. This application is founded on the premise that stimulant use disorder in humans can be studied using preclinical assays of drug-vs-food choice that model clinical aspects of behavioral misallocation and decision making between concurrently available drugs and an alternative nondrug reinforcer. We propose to determine 1) VU0364572 effects on cocaine-food and cocaine-social choice, 2) VU0364572 effects on methamphetamine-food and methamphetamine-social choice, and 3) VU0364572 effects on nucleus accumbens and prefrontal cortex dopamine release using dLight.

这项新的 R01 申请提出了一系列系统实验，重点关注药物选择程序 雄性和雌性大鼠评估毒蕈碱乙酰胆碱受体 (mAChR)1 激动剂 VU0364572 作为 用于治疗可卡因和甲基苯丙胺使用障碍的候选药物。此应用程序已创建 前提是可以使用药物与食物的临床前分析来研究人类兴奋剂使用障碍 选择模拟行为错配和同时进行决策的临床方面 可用的药物和替代的非药物强化剂。我们建议确定 1) VU0364572 对 可卡因-食物和可卡因-社会选择，2) VU0364572 对甲基苯丙胺-食物和可卡因-社会选择的影响 甲基苯丙胺-社会选择，以及 3) VU0364572 对伏隔核和前额皮质的影响 使用 dLight 释放多巴胺。