MR Spectroscopy and Behavior after Clinically Relevant Administration of MDMA

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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.