Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the Fyn Kinase Inhibitor Drug, Saracatinib.

酒精中毒脆弱性的功能神经影像学：使用 Fyn 激酶抑制剂药物 Saracatinib 探测谷氨酸和奖励。

• 批准号: 9277336
• 负责人: GODFREY D PEARLSON
• 金额: $ 20.93万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9277336
• 关键词: Affect; Alcohol dependence; Alcoholism; Alcohols; Animals; Attenuated; Behavioral; Brain; Clinical; Corpus striatum structure; Cues; Cyclic AMP-Dependent Protein Kinases; Detection; Doctor of Medicine; Dopamine; Dorsal; Dose; Double-Blind Method; Equilibrium; Excitatory Amino Acid Antagonists; Executive Dysfunction; Family; First Degree Relative; Functional Magnetic Resonance Imaging; Functional disorder; Glutamate Receptor; Glutamates; Goals; Human; Hyperactive behavior; Impact evaluation; Impairment; Impulsivity; Incentives; Individual; Learning; Link; Measures; Memantine; Motivation; N-Methylaspartate; Neurotransmitters; Nucleus Accumbens; Outcome; Parents; Participant; Pathway interactions; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Phosphotransferases; Placebo Control; Placebos; Punishment; Randomized; Receptor Signaling; Recording of previous events; Reporting; Research Design; Rest; Rewards; Risk; Role; Series; Signal Pathway; Signal Transduction; Stimulus; Suggestion; Technology; Testing; Therapeutic Effect; alcohol craving; alcohol cue; alcohol use disorder; classical conditioning; connectome; cue reactivity; drinking; executive function; habituation; kinase inhibitor; neuroimaging; receptor function; response; translational neuroscience

Project 2: Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the Fyn Kinase Inhibitor Drug, Saracatinib Godfrey Pearlson, M.D. Abstract This project will test the impact of a direct manipulation of a specific, alcoholism risk-relevant mechanism involving intracellular signaling, on functional MRI-measured human reward brain circuit function. It tests the dose-related effects of the Fyn kinase (Fyn) inhibitor drug, saracatinib (AZD0530) in a placebo-controlled, double-blind, randomized, counterbalanced study design. All proposed aims for Project 2 compare family history positive for alcoholism (FHP; i.e., affected parent plus other close relatives, N=40) to matched family history negative (FHN; i.e., no affected first-degree relative, N=40) participants on four fMRI tasks, with the goal of clarifying the interplay of the neurotransmitters dopamine and glutamate via protein kinase A- related signaling pathways in reward circuit dysfunction associated with familial risk for alcoholism.

项目 2：酒精中毒脆弱性的功能神经影像学：探索谷氨酸和 奖励，使用 Fyn 激酶抑制剂药物 Saracatinib 戈弗雷·珀尔森，医学博士 抽象的 该项目将测试直接操纵特定的、与酗酒风险相关的因素的影响 涉及细胞内信号传导的机制，对功能性 MRI 测量的人类奖励大脑的影响 电路功能。它测试 Fyn 激酶 (Fyn) 抑制剂药物的剂量相关效应， saracatinib (AZD0530) 安慰剂对照、双盲、随机、平衡 研究设计。项目 2 的所有拟议目标都比较酗酒阳性的家族史 （FHP；即受影响的父母加上其他近亲，N=40）与匹配的家族史阴性 （FHN；即没有受影响的一级亲属，N=40）参与者执行四项 fMRI 任务，目标是 阐明神经递质多巴胺和谷氨酸通过蛋白激酶 A 的相互作用 与家族风险相关的奖赏回路功能障碍的相关信号通路 酗酒。