Nitrous Oxide and Cortico-Limbic Function in Aggression

项目摘要 在这个应用中，我们建议建立在先前关于谷氨酸在冲动中的作用的工作的基础上 攻击性。来自我们实验室和其他实验室的临床前动物研究和最近的人类研究都支持 认为谷氨酸是促进攻击行为的重要调节剂的假说。在这项研究中，我们 建议使用FDA批准的谷氨酸能调节剂一氧化二氮(N2O)来确定N2O是否具有 使以前与冲动攻击行为相关的皮质-边缘回路正常化的能力 人类。冲动的攻击性和健康的非攻击性对照，研究参与者将经历两次 吸入方案(50%N2O/50%O2为有效吸入，50%氮气/50%O2为对照)至少隔开一个 并在每次吸入性研究后24小时进行功能磁共振成像扫描。如果这种机械论的研究 表明吸入N2O可以使这些回路的功能正常化，N2O可能代表着 作为反攻击性代理人的候选人。

Project Summary In this application, we propose to build on previous work regarding the role of glutamate in impulsive aggression. Both preclinical animal studies and recent human studies from our labs and other labs support the hypothesis that glutamate is an important modulator that facilitates aggressive behavior. In this study, we propose to use an FDA approved glutamatergic modulator, Nitrous Oxide (N2O), to determine if N2O has the ability to normalize cortico-limbic circuits previously associated with impulsive aggressive behavior in humans. Impulsive aggressive, and healthy non-aggressive control, study participants will undergo two inhalation protocols (50% N2O / 50% O2 as active and 50% N2 / 50% O2 as control) separated by at least one week and undergo an fMRI Scan 24 hours after each inhalation study session. If this mechanistic study demonstrates that N2O inhalation can normalize the functioning of these circuits, N2O may represent a candidate as an anti-aggressive agent.