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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要在此应用中，我们建议以先前关于谷氨酸在冲动中的作用的工作为基础侵略。我们的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。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。冲动攻击性和健康的非攻击性控制，研究参与者将经历两种吸入方案（50% N2O / 50% O2 作为活性剂，50% N2 / 50% O2 作为对照）至少间隔一个每周并在每次吸入研究课程后 24 小时进行 fMRI 扫描。如果这个机制研究表明吸入 N2O 可以使这些回路的功能正常化，N2O 可能代表作为反侵略代理人的候选人。