This is a revised K02 application. Dr. Stephen L. Dewey is a neuroanatomist and a senior scientist. He has a distinguished record in neuroimaging, microdialysis and medications development for drug abuse. His early work focused on imaging neurotransmitter interactions. These pioneering studies produced a paradigm shift that represents one of the most effective applications of PET research today. As a result, Dr. Dewey identified gamma vinyl-GABA, (GVG, vigabatrin) for the treatment of drug abuse. Following the generation of an unprecedented published preclinical database, which produced 9 U.S. patents (1 additional pending), he designed and conducted 2 open labeled clinical trials in adult cocaine and methamphetamine abusers. These trials suggested clinical efficacy and demonstrated visual safety, while also serving as the foundation for 2 Investigative New Drug (IND) applications, recently accepted by the FDA, for Phase I and II clinical trials. Dr. Dewey has successfully graduated 3 doctoral students and is currently a thesis advisor for three additional doctoral candidates as well as being a mentor to several junior scientists. In 1994, Dr. Dewey initiated an outreach program to adolescents that reached more than 55,000 children last year alone (more than 300,000 since its inception), motivating his new research initiative in inhalant abuse. This K02 will release Dr. Dewey from teaching and provide 60% salary support, which will result in at least 75% protected time to focus on the new molecular entity, S- (+)-GVG, for the treatment of adult and adolescent methamphetamine or inhalant abuse. This application proposes 2 synergistic goals: (1) Research (60%);to identify optimal treatment regimens with the new molecular entity, S- (+)-GVG, for adult and adolescent methamphetamine or inhalant abuse using the identical strategies he successfully employed with GVG and (2);Mentoring and outreach (15%): to mentor junior investigators, post-doctoral fellows, and graduate and undergraduate students while continuing his extensive outreach program. This research benefits from collaborators at BNL, Stony Brook Univ, New York Univ, St. Johns Univ, and NIDA intramural. Thus, the objectives of this application are to identify optimal treatment regimens for methamphetamine or inhalant abuse while inspiring, teaching, and encouraging young scientists across disciplines to investigate the major public health consequences created by adolescent and adult drug abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA022346-06
Application #
8085904
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Acri, Jane
Project Start
2007-09-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
6
Fiscal Year
2011
Total Cost
$134,136
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna et al. (2017) Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement. Neuropsychopharmacology 42:1841-1849
Santoro, Giovanni C; Carrion, Joseph; Dewey, Stephen L (2017) Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal. J Alcohol Drug Depend 5:
Santoro, Giovanni C; Shukla, Samarth; Patel, Krishna et al. (2016) A Novel Strategy for Attenuating Opioid Withdrawal in Neonates. J Addict Res Ther 7:
Pan, Yue; Gerasimov, Madina R; Kvist, Trine et al. (2012) (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent ?-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. J Med Chem 55:357-66
Mirrione, Martine M; Konomos, Dorothy K; Gravanis, Iordanis et al. (2010) Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice. Neurobiol Dis 39:85-97
DeMarco, Amy; Dalal, Reema M; Pai, Jessica et al. (2009) Racemic gamma vinyl-GABA (R,S-GVG) blocks methamphetamine-triggered reinstatement of conditioned place preference. Synapse 63:87-94
Schiffer, Wynne K; Liebling, Courtney N B; Reiszel, Corinne et al. (2009) Cue-induced dopamine release predicts cocaine preference: positron emission tomography studies in freely moving rodents. J Neurosci 29:6176-85
Brodie, Jonathan D; Case, Brady G; Figueroa, Emilia et al. (2009) Randomized, double-blind, placebo-controlled trial of vigabatrin for the treatment of cocaine dependence in Mexican parolees. Am J Psychiatry 166:1269-77
Lee, Dianne E; Pai, Jennifer; Mullapudui, Uma et al. (2008) The effects of inhaled acetone on place conditioning in adolescent rats. Pharmacol Biochem Behav 89:101-5
DeMarco, Amy; Dalal, Reema M; Kahanda, Milan et al. (2008) Subchronic racemic gamma vinyl-GABA produces weight loss in Sprague Dawley and Zucker fatty rats. Synapse 62:870-2

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