MR Spectroscopy and Behavior after Clinically Relevant Administration of MDMA

描述（由申请人提供）：本K 0 I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。该研究计划旨在调查兴奋剂诱导的行为与质子磁共振波谱（'HMRS）确定的伴随神经化学特征之间的潜在关联。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。培训和研究活动由Matthew P. Galloway博士指导。职业发展计划包括系列研讨会，教学法，科学会议，手稿审查/写作，负责任的研究行为，并提高研究技能。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依赖性结果的临床相关因素。在11.7 T下的专门版本的'HMRS将用于测量局部GABA、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。将采用HPLC法测定单胺，采用ELISA法测定血皮质酮。将在先前接受过MDMA给药后运动、焦虑和抑郁样行为试验的大鼠中测量神经化学效应。为了评估诱发因素，将研究MDMA在反复不可预测的压力或大麻预处理后的影响。此外，MDMA对体内'HMRS的纵向影响将与共同导师Gregory J.摩尔，医学博士合作进行探索。博士由于MDMA对5-羟色胺神经元具有神经毒性，多药使用和共病精神疾病使临床研究复杂化，并且重复使用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，MDMA对行为和单胺的影响与1HMRS谱有直接的翻译潜力。

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.