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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA024760-05
Application #
8314101
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Frankenheim, Jerry
Project Start
2008-08-01
Project End
2013-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$154,750
Indirect Cost
$11,463
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Cox, Brittney M; Shah, Mrudang M; Cichon, Teri et al. (2014) Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. Prog Neuropsychopharmacol Biol Psychiatry 48:229-35
Perrine, Shane A; Ghoddoussi, Farhad; Michaels, Mark S et al. (2014) Ketamine reverses stress-induced depression-like behavior and increased GABA levels in the anterior cingulate: an 11.7 T 1H-MRS study in rats. Prog Neuropsychopharmacol Biol Psychiatry 51:9-15
Church, Michael W; Zhang, Jinsheng S; Langford, Megan M et al. (2013) 'Ecstasy' enhances noise-induced hearing loss. Hear Res 302:96-106
Eagle, Andrew L; Fitzpatrick, Chris J; Perrine, Shane A (2013) Single prolonged stress impairs social and object novelty recognition in rats. Behav Brain Res 256:591-7
Eagle, Andrew L; Knox, Dayan; Roberts, Megan M et al. (2013) Single prolonged stress enhances hippocampal glucocorticoid receptor and phosphorylated protein kinase B levels. Neurosci Res 75:130-7
Eagle, Andrew L; Perrine, Shane A (2013) Methamphetamine-induced behavioral sensitization in a rodent model of posttraumatic stress disorder. Drug Alcohol Depend 131:36-43
Murnane, Kevin Sean; Perrine, Shane Alan; Finton, Brendan James et al. (2012) Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry. Psychopharmacology (Berl) 220:495-508
Cox, Brittney M; Alsawah, Fares; McNeill, Peter C et al. (2011) Neurochemical, hormonal, and behavioral effects of chronic unpredictable stress in the rat. Behav Brain Res 220:106-11
Perrine, Shane A; Nayak, Raghavendra; Bharadwaj, Aditya S et al. (2011) Effect of substance abuse on defibrillation threshold in patients with implantable cardioverter-defibrillator. Pacing Clin Electrophysiol 34:193-9
Perrine, Shane A; O'Leary-Moore, Shonagh K; Galloway, Matthew P et al. (2011) Binge toluene exposure alters glutamate, glutamine and GABA in the adolescent rat brain as measured by proton magnetic resonance spectroscopy. Drug Alcohol Depend 115:101-6

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