MR Spectroscopy and Behavior after Clinically Relevant Administration of MDMA

临床相关施用 MDMA 后的 MR 能谱和行为

• 批准号: 8106269
• 负责人: Shane Alan Perrine
• 金额: $ 15.57万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8106269
• 关键词: Abstinence; Acute; Agonist; Aminobutyric Acids; Amygdaloid structure; Animals; Anterior; Anxiety; Appointment; Behavior; Behavioral; Blood; Brain; Cannabis; Clinical; Clinical Trials; Cognitive deficits; Collaborations; Corpus striatum structure; Corticosterone; Dehydration; Dependency; Desire for food; Developed Countries; Development Plans; Dissection; Doctor of Medicine; Doctor of Philosophy; Dose; Drug usage; Empathy; Enzyme-Linked Immunosorbent Assay; Exposure to; Feeling; Glutamate Metabolism Pathway; Glutamates; Glutamine; Goals; Hallucinogens; High Pressure Liquid Chromatography; Hippocampus (Brain); Human; Implant; Investigation; Lead; Lesion; Long-Term Effects; Magnetic Resonance Spectroscopy; Manuscripts; Marijuana; Marijuana Smoking; Measures; Mediating; Mental Depression; Mental disorders; Mentors; Mentorship; Modeling; Motor Activity; N-acetylaspartate; Neurobiology; Neurons; Outcome; Paranoia; Patient Self-Report; Pattern; Pharmaceutical Preparations; Predisposing Factor; Prefrontal Cortex; Principal Investigator; Property; Protons; Public Health; Rattus; Recreational Drugs; Research; Research Activity; Series; Serotonin; Signal Transduction; Sleep; Stomach; Stress; Swimming; Testing; Thirst; Time; Training; Training Activity; Work; Writing; addiction; behavior test; behavioral sensitization; cannabinoid receptor; carbene; career development; clinically relevant; design; ecstasy; exhaustion; frontal lobe; gamma-Aminobutyric Acid; in vivo; killings; meetings; monoamine; neurochemistry; neurotoxic; neurotoxicity; programs; response; responsible research conduct; skills; Abstinence; Acute; Agonist; Aminobutyric Acids; Amygdaloid structure; Animals; Anterior; Anxiety; Appointment; Behavior; Behavioral; Blood; Brain; Cannabis; Clinical; Clinical Trials; Cognitive deficits; Collaborations; Corpus striatum structure; Corticosterone; Dehydration; Dependency; Desire for food; Developed Countries; Development Plans; Dissection; Doctor of Medicine; Doctor of Philosophy; Dose; Drug usage; Empathy; Enzyme-Linked Immunosorbent Assay; Exposure to; Feeling; Glutamate Metabolism Pathway; Glutamates; Glutamine; Goals; Hallucinogens; High Pressure Liquid Chromatography; Hippocampus (Brain); Human; Implant; Investigation; Lead; Lesion; Long-Term Effects; Magnetic Resonance Spectroscopy; Manuscripts; Marijuana; Marijuana Smoking; Measures; Mediating; Mental Depression; Mental disorders; Mentors; Mentorship; Modeling; Motor Activity; N-acetylaspartate; Neurobiology; Neurons; Outcome; Paranoia; Patient Self-Report; Pattern; Pharmaceutical Preparations; Predisposing Factor; Prefrontal Cortex; Principal Investigator; Property; Protons; Public Health; Rattus; Recreational Drugs; Research; Research Activity; Series; Serotonin; Signal Transduction; Sleep; Stomach; Stress; Swimming; Testing; Thirst; Time; Training; Training Activity; Work; Writing; addiction; behavior test; behavioral sensitization; cannabinoid receptor; carbene; career development; clinically relevant; design; ecstasy; exhaustion; frontal lobe; gamma-Aminobutyric Acid; in vivo; killings; meetings; monoamine; neurochemistry; neurotoxic; neurotoxicity; programs; response; responsible research conduct; skills

DESCRIPTION (provided by applicant): This K0I proposal is intended to provide support and protected time for the PI to execute a research plan designed as both an original scientific investigation as well as a training vehicle. The research plan aims to investigate potential associations between stimulant-induced behaviors and the attendant neurochemical profile determined with proton magnetic resonance spectroscopy ('HMRS). It is anticipated that the PI will acquire the skills to become an independent neuroscientist and ultimately achieve the long-term goal of a tenure-track academic appointment studying addiction neurobiology. Training and research activities are under the mentorship of Matthew P. Galloway, Ph.D. The career development plan includes seminar series, didactics, scientific meetings, manuscript reviewing/writing, responsible research conduct, and enhanced research skills. The research plan will study the behavioral and neurochemical dose-effects of MDMA (3,4 methylene-dioxymethamphetamine; ecstasy) as well as clinically-relevant factors that may influence MDMA-dependent outcomes. A specialized version of 'HMRS at 11.7 T will be used to measure regional GAB A, N-acetylaspartate, glutamate, as well as a host of other MR-visible neurochemical levels. HPLC will be used to measure monoamines and ELISA for blood corticosterone. Neurochemical effects will be measured in rats previously tested for locomotor, anxiety, and depression-like behaviors following MDMA. To assess predisposing factors, the effects of MDMA following repeated unpredictable stress or cannabis pretreatment will be studied. Also, the longitudinal effects of MDMA on in vivo 'HMRS will be explored in collaboration with co-mentor Gregory J. Moore, M.D. Ph.D. Since MDMA is neurotoxic to serotonin neurons, polydrug use and comorbid psychiatric conditions complicate clinical investigations and repeated MDMA use is associated with cognitive deficits in humans, the proposed research is highly relevant to public health. Moreover, relating MDMA's effects on behavior and monoamines to 1HMRS profiles has direct translational potential.

描述（由申请人提供）：该K0I提案旨在为PI提供支持和保护时间，以执行设计为原始科学研究和培训工具的研究计划。该研究计划旨在研究刺激性诱导的行为与由质子磁共振光谱（'HMRS）确定的随之而来的神经化学谱之间的潜在关联。预计PI将获得成为独立神经科学家的技能，并最终实现了研究成瘾神经生物学的终身学术任命的长期目标。培训和研究活动是在Matthew P. Galloway博士的指导下。职业发展计划包括研讨会系列，教学，科学会议，手稿审查/写作，负责任的研究行为以及增强的研究技能。该研究计划将研究MDMA的行为和神经化学剂量效应（3,4-甲基二甲基甲基苯丙胺；摇头丸）以及可能影响MDMA依赖性结果的临床相关因素。 11.7 T时的HMR的专业版本将用于测量区域GAB A，N-乙酰天冬氨酸，谷氨酸以及其他许多可见的神经化学水平。 HPLC将用于测量血性皮质酮的单胺和ELISA。 MDMA后，将在先前测试的运动，焦虑和类似抑郁的行为的大鼠中测量神经化学作用。为了评估诱发因素，将研究重复不可预测的压力或大麻预处理后MDMA的影响。此外，将与Co-intor Gregory J. Moore，M.D。Ph.D.一起探索MDMA对体内HMR的纵向影响。由于MDMA对5-羟色胺神经元具有神经毒性，因此多药的使用和合并症的精神病疾病会使临床研究复杂化，并且反复使用MDMA与人类认知缺陷有关，因此拟议的研究与公共卫生高度相关。此外，将MDMA对行为和单胺的影响与1HMRS轮廓有关，具有直接的转化潜力。