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

项目2：酒精中毒易损性的功能神经成像：探测谷氨酸和 奖励，使用Fyn激酶抑制剂药物沙拉卡替尼 Godfrey Pearlson医学博士 摘要 这个项目将测试直接操纵特定的、与酒精中毒风险相关的影响 功能磁共振测量的人类奖赏脑涉及细胞内信号的机制 电路功能。它测试Fyn激酶(Fyn)抑制剂药物的剂量相关效应， 安慰剂对照、双盲、随机、平衡的沙拉卡替尼(AZD0530) 研究设计。项目2的所有拟议目标都将家族史与酗酒呈阳性进行比较 (FHP；即受影响的父母加上其他近亲，N=40)匹配的家族史阴性 (FHN；即没有受影响的一级亲属，N=40)参与四项fMRI任务，目标是 通过蛋白激酶A阐明神经递质多巴胺和谷氨酸的相互作用-- 奖赏回路功能障碍的相关信号通路与家族性心脏病的风险 酗酒。

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.