Nitrous Oxide and Cortico-Limbic Function in Aggression

攻击行为中的一氧化二氮和皮质边缘功能

• 批准号: 9896211
• 负责人: EMIL Frank COCCARO
• 金额: $ 19.5万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896211
• 关键词: Acute; Aggressive behavior; Amygdaloid structure; Anesthetics; Anger; Animal Model; Animals; Antidepressive Agents; Behavior; Behavioral; Brain-Derived Neurotrophic Factor; Cell physiology; Cerebrospinal Fluid; Chronic; Clinical; Complex; Coupled; Craniocerebral Trauma; DSM-V; Dendritic Spines; Depressed mood; Disease; Emotional; Emotions; Event; FDA approved; Face; Functional Magnetic Resonance Imaging; Glutamates; Hour; Human; Impulsivity; Individual; Inflammatory; Infusion procedures; Inhalation; Intermittent Explosive Disorders; Intoxication; Ketamine; Lead; Measures; Mental Depression; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Natural regeneration; Neuroglia; Neurotransmitters; Nitrous Oxide; Participant; Pharmaceutical Preparations; Phase; Play; Population; Protocols documentation; Psychotic Disorders; Recording of previous events; Recurrence; Rest; Role; Series; Serotonin; Signal Transduction; System; Testing; Thinking; Time; Treatment Efficacy; Withdrawal; Work; antidepressant effect; cortico-limbic circuits; cytokine; functional MRI scan; human subject; improved; improved functioning; infancy; information processing; interest; neurochemistry; neuroimaging; pre-clinical; response; social; stem; treatment-resistant depression

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.

项目摘要 在这个应用中，我们建议建立在以前的工作，关于谷氨酸在冲动中的作用， 侵略我们实验室和其他实验室的临床前动物研究和最近的人体研究都支持 假设谷氨酸是促进攻击行为的重要调节剂。本研究 建议使用FDA批准的一氧化二氮（N2 O）调节剂，以确定N2 O是否具有 使先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，和健康的非攻击性控制，研究参与者将经历两个 吸入方案（50%N2O/50%O2作为活性物质，50%N2/50%O2作为对照）， 每周，并在每次吸入研究后24小时进行fMRI扫描。如果这个机械研究 表明N2 O吸入可以使这些回路的功能正常化，N2 O可能代表一种 作为抗攻击剂的候选人。