This is the second competing renewal of our Program Project Grant, """"""""Drugs of Abuse: Role of Protein phosphorylation"""""""" (DA 10044), which was initially funded in 1996 and again in 2001. The grant has been highly successful based on research productivity and initiation of new research projects. The overall objective of the Program Project Grant remains the same as the original, namely, to elucidate the molecular basis of the actions of drugs of abuse, particularly psychostimulants, in the dorsal striatum and nucleus accumbens. The addictive properties of drugs of abuse such as psychostimulants depend on their ability to augment dopamine neurotransmission in the basal ganglia. The Program Project Grant is organized in four Projects, a Scientific Core and an Administrative Core. The Administrative Core staff will support the integration of the researchers and institutions involved in the Program Project Grant. The main goal of the Scientific Core is to provide a research and technical support facility for all of the Program projects. Responsibilities of the Scientific Core will include the creation, characterization, and breeding of genetically altered animals;the design and execution of yeast two-hybrid studies;the production and maintenance of key reagents stocks and new reagents;and the performance of certain routine tasks required to accomplish the studies described in Projects I-IV. Project I, """"""""Psychostimulants and dendritic spines,"""""""" will focus on the role five regulators of actin dynamics play as targets of psychostimulants in the dendritic spines. Project II, """"""""The Role of DARPP-32, CK1, and CK2 in Mediating the Molecular and Behavioral Effects of Drugs of Abuse,"""""""" will extend previous studies of four key phosphorylation sites of DARPP-32 upon in vivo administration of drugs of abuse and chronic exposure to drugs of abuse. Project III, """"""""Striatal Phosphoproteins and the Actions of Psychostimulants,"""""""" which will be a subcontract carried out at Yale University School of Medicine, study the role(s) of RCS and ARPP-16 in mediating or modulating the actions of psychostimulants as well as study the roles of the three isoforms of PP1 (PPla, P and y) in the actions of psychostimulants. Project IV, """"""""The Role of GPCR-interacting Proteins in the Actions of Pscyhostimulants,"""""""" will utilize yeast two-hybrid screening to further investigate the multiple intracellular signaling pathways of GPCR and its protein-interacting subunits in mediating actions of cocaine, D-amphetamine, ecstasy and caffeine.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-RXL-E (18))
Program Officer
Satterlee, John S
Project Start
Project End
Budget Start
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Support Year
Fiscal Year
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Rockefeller University
Other Basic Sciences
Other Domestic Higher Education
New York
United States
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Ceglia, Ilaria; Lee, Ko-Woon; Cahill, Michael E et al. (2017) WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine. Proc Natl Acad Sci U S A 114:1395-1400
Milosevic, Ana; Liebmann, Thomas; Knudsen, Margarete et al. (2017) Cell- and region-specific expression of depression-related protein p11 (S100a10) in the brain. J Comp Neurol 525:955-975
Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko et al. (2017) ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase). J Neurosci 37:2709-2722
Seo, J-S; Zhong, P; Liu, A et al. (2017) Elevation of p11 in lateral habenula mediates depression-like behavior. Mol Psychiatry :
Musante, Veronica; Li, Lu; Kanyo, Jean et al. (2017) Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition. Elife 6:
Seo, J-S; Wei, J; Qin, L et al. (2017) Cellular and molecular basis for stress-induced depression. Mol Psychiatry 22:1440-1447
Rapanelli, Maximiliano; Frick, Luciana R; Horn, Kyla D et al. (2016) The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons. J Biol Chem 291:21042-21052
Virk, Michael S; Sagi, Yotam; Medrihan, Lucian et al. (2016) Opposing roles for serotonin in cholinergic neurons of the ventral and dorsal striatum. Proc Natl Acad Sci U S A 113:734-9
Lee, K-W; Westin, L; Kim, J et al. (2015) Alteration by p11 of mGluR5 localization regulates depression-like behaviors. Mol Psychiatry 20:1546-56
Lazenka, Matthew F; Tomarchio, Aaron J; Lichtman, Aron H et al. (2015) Role of Dopamine Type 1 Receptors and Dopamine- and cAMP-Regulated Phosphoprotein Mr 32 kDa in ?9-Tetrahydrocannabinol-Mediated Induction of ?FosB in the Mouse Forebrain. J Pharmacol Exp Ther 354:316-27

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