Linking serotonin and memory functions in MDMA users by concurrent EEG and fMRI

通过并发脑电图和功能磁共振成像将摇头丸使用者的血清素和记忆功能联系起来

• 批准号: 7488414
• 负责人: JAMES C ELIASSEN
• 金额: $ 15.8万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488414
• 关键词: Affect; Animal Experimentation; Anxiety; Attention; Auditory Evoked Potentials; Axon; Behavior; Brain; California; Cognition; Cognitive; Data; Dependence; Development; Dopamine; Drug abuse; Electroencephalography; Environment; Europe; Evaluation; Event-Related Potentials; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Health; Human; Illicit Drugs; Image; Lateral; Learning; Link; Loudness; Maps; Marijuana; Measures; Medial; Medical; Memory; Memory impairment; Mental Depression; Mentored Research Scientist Development Award; Mentors; Mood Disorders; National Institute of Drug Abuse; Neurons; Neurotransmitters; Pattern; Performance; Play; Post-Traumatic Stress Disorders; Prevalence; Prevention; Primates; Public Health; Punishment; Rate; Reporting; Research; Research Training; Rewards; Rodent; Role; Rosa; Scientist; Serotonin; Source; Stress; Students; Substance Addiction; Substance Use Disorder; Substance abuse problem; System; Techniques; Testing; Therapeutic; United States; Universities; Verbal Learning; Work; auditory stimulus; behavior measurement; carbene; career; classical conditioning; college; disturbance in affect; dopamine system; ecstasy; forgetting; frontal lobe; memory process; memory recognition; mood regulation; neurotoxic; neurotoxicity; novel; prevent; programs; relating to nervous system; research study; systems research; young adult

DESCRIPTION (provided by applicant): This revised NIDA Mentored Research Scientist Development (K01) Award application will support Dr. James Eliassen's long-term career objective of developing an independent substance abuse research program that examines the link between learning and memory functions, monoaminergic transmitter systems and substance abuse. Specifically, Dr. Eliassen will examine the effect of human recreational MDMA use on learning and memory and the link between cognitive and serotonergic function with electroencephalography techniques (EEG) and simultaneous functional magnetic resonance imaging (fMRI). MDMA is the second most widely used illicit substance after marijuana, and animal research indicates that MDMA damages serotonergic neurons and chronically impairs behavior. Since the effects in humans appear to be similar and up to 10% of young adults have tried MDMA any negative consequences constitute a significant public health concern. Some ambiguity exists in the link between human MDMA use, serotonergic dysfunction, and memory impairment, and this issue needs to be clarified through further research so that the dangers of MDMA use can be clearly appreciated by the public. Specifically, in order to substantiate the claim that MDMA impairs learning and memory through neurotoxic sequelae Dr. Eliassen will record evoked and event- related potential EEG (EP, ERP) simultaneously with fMRI in MDMA users. He will examine whether the EEG and fMRI markers of learning and memory processes are altered by MDMA use in correspondence to changes in serotonergic function, as measured by the loudness dependence of the late auditory evoked potential N1 (LDAEP). Additionally, Dr. Eliassen will combine EEG and fMRI data into multi-modal dynamic brain activity maps in order to confirm that mnemonic and serotonergic dysfunction arise from the same temporal and spatial neural sources in the brain. We predict that if MDMA's neurotoxic actions are responsible for learning and memory impairments we will observe corresponding changes in the electrophysiological, fMRI, and behavioral measures of cognition and the LDAEP measure of serotonin function in recreational MDMA users but not controls. This research will help confirm and further characterize the mechanism by which MDMA ostensibly causes learning and memory impairments due to its neurotoxic actions on the serotonin system. The proposed research and training plan and the productive research environment of the University of Cincinnati Center for Imaging Research will enable the candidate to develop an independent substance abuse research career that examines the link between learning and memory, monoaminergic transmitters (e.g., serotonin), and substance abuse.

描述（由申请人提供）：经修订的NIDA指导研究科学家发展（K01）奖项将支持James Eliassen博士的长期职业目标，即制定独立的药物滥用研究计划，该计划研究学习与记忆功能之间的联系系统和药物滥用。具体而言，Eliassen博士将研究人类娱乐性MDMA对学习和记忆的影响以及认知和血清素能功能与脑电图技术（EEG）和同时功能磁共振成像（FMRI）之间的联系。 MDMA是仅次于大麻的第二大使用的非法物质，动物研究表明MDMA会损害血清素能神经元，并长期损害行为。由于人类的影响似乎相似，并且多达10％的年轻人尝试了MDMA，任何负面后果都构成了重大的公共卫生问题。人类MDMA使用，血清素能功能障碍和记忆障碍之间存在一些歧义，并且需要通过进一步的研究来阐明这个问题，以便公众可以清楚地赞赏MDMA使用的危险。具体而言，为了证实MDMA通过神经毒性后遗症损害学习和记忆的说法，Eliassen博士将与MDMA用户同时与fMRI同时记录诱发的诱发和与事件相关的潜在EEG（EP，ERP）。他将检查学习和记忆过程的脑电图和fMRI标记是否通过MDMA使用改变了与血清素能功能的变化相对应的，如晚期听觉引起的潜在N1（LDAEP）的响度依赖性所测量。此外，Eliassen博士将将脑电图和fMRI数据结合到多模式动态大脑活性图中，以确认助记素和血清素能功能障碍是由大脑中相同的时间和空间神经来源引起的。我们预测，如果MDMA的神经毒性作用负责学习和记忆力障碍，我们将观察到认知的电生理，fMRI和行为度量的相应变化，以及在娱乐性MDMA使用者中的5-羟色胺功能的LDAEP度量。这项研究将有助于确认并进一步表征MDMA表面上由于其神经毒性对5-羟色胺系统的神经毒性作用而导致学习和记忆障碍的机制。辛辛那提大学成像研究中心的拟议研究与培训计划以及生产性研究环境将使候选人能够开发独立的药物滥用研究职业，该职业研究学习与记忆与记忆，单胺能发射器（例如，羟色胺）之间的联系药物滥用。