MR Spectroscopy and Behavior after Clinically Relevant Administration of MDMA

描述(由申请人提供)：本K0I提案旨在为PI执行既是原始科学调查又是培训工具的研究计划提供支持和保护时间。该研究计划旨在调查兴奋剂诱导的行为与质子磁共振波谱(‘HMRS)确定的伴随的神经化学特征之间的潜在联系。预计PI将获得成为一名独立神经科学家的技能，并最终实现研究成瘾神经生物学的终身教职学术任命的长期目标。培训和研究活动在马修·P·加洛韦博士的指导下进行。职业发展计划包括系列研讨会、教学、科学会议、手稿审查/写作、负责任的研究行为和增强研究技能。该研究计划将研究MDMA(3，4-亚甲基二氧基甲基苯丙胺；摇头丸)的行为和神经化学剂量效应，以及可能影响MDMA依赖结果的临床相关因素。一个专门版本的11.7T的‘HMRS将被用来测量区域GAB A，N-乙酰天冬氨酸，谷氨酸，以及许多其他MR可见的神经化学水平。将用高效液相色谱法测定单胺类物质，用酶联免疫吸附试验测定血液皮质酮。神经化学效应将在先前测试MDMA后的运动、焦虑和抑郁样行为的大鼠中进行测量。为了评估诱发因素，将研究在反复不可预测的压力或大麻预处理后使用MDMA的效果。此外，MDMA对体内HMRS的纵向影响将与共同导师格雷戈里·J·摩尔医学博士合作进行探索。由于MDMA对5-羟色胺神经元具有神经毒性，多药使用和并存的精神疾病使临床研究复杂化，反复使用MDMA与人类认知缺陷有关，因此拟议的研究与公共健康高度相关。此外，将MDMA对行为和单胺的影响与1HMRS谱相关联具有直接的翻译潜力。

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.