This is the third competing renewal of our Program Project Grant, "Drugs of Abuse: Role of Protein Phosphorylation" (DA010044), which was initially funded in 1996 and most recently in 2006. 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 Program Project Grant is organized into three Projects, a Scientific Core and an Administrative Core. The Administrative Core 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 research and technical support for all of the 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 1-3. Project 1, "Cell type- and region-specific studies of psychostimulants and dendritic spines" will focus on the role of Cdk5 and WAVE1, regulators of actin dynamics in the dendritic spines. Project 2, "The role of the mGluR5/CK1-CK2/DARPP-32 pathway in mediating the effects of psychostimulants," will extend previous studies of novel signaling pathways that regulate DARPP-32 function. Project 3, "Striatal Phosphoproteins and the Actions of Psychostimulants," which will be a subcontract carried out at Yale University School of Medicine, will study the role of Rap GTPase, and its modulators Rap1GAP and Epac2 in the actions of psychostimulants, as well as study the role of novel isoforms of PP2A in the actions of psychostimulants. Results from the three Projects will complement each other. In addition, there will be a significant level of collaboration between the three Projects, as well as close interaction of the three Projects with the Scientific Core.

Public Health Relevance

Together the three Projects of the Program Project Grant will carry out innovative research that will lead to elucidation of the molecular pathways through which drugs of abuse act in the brain, and to an increased likelihood that therapeutic agents will be developed that will prevent or reverse molecular adaptations within these pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
5P01DA010044-17
Application #
8231286
Study Section
Special Emphasis Panel (ZRG1-MDCN-G (51))
Program Officer
Satterlee, John S
Project Start
1997-03-01
Project End
2016-02-29
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
17
Fiscal Year
2012
Total Cost
$1,473,385
Indirect Cost
$497,729
Name
Rockefeller University
Department
Other Basic Sciences
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Milosevic, Ana; Liebmann, Thomas; Knudsen, Margarete et al. (2016) Cell- and region-specific expression of depression-related protein p11 (S100a10) in the brain. J Comp Neurol :
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
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
Liu, Ruijie; Correll, Robert N; Davis, Jennifer et al. (2015) Cardiac-specific deletion of protein phosphatase 1β promotes increased myofilament protein phosphorylation and contractile alterations. J Mol Cell Cardiol 87:204-13
Uematsu, Ken; Heiman, Myriam; Zelenina, Marina et al. (2015) Protein kinase A directly phosphorylates metabotropic glutamate receptor 5 to modulate its function. J Neurochem 132:677-86
Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas et al. (2015) DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons. Nat Commun 6:10099
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
Yamagata, Yoko; Nairn, Angus C (2015) Contrasting features of ERK1/2 activity and synapsin I phosphorylation at the ERK1/2-dependent site in the rat brain in status epilepticus induced by kainic acid in vivo. Brain Res 1625:314-23
Plattner, Florian; Hayashi, Kanehiro; Hernández, Adan et al. (2015) The role of ventral striatal cAMP signaling in stress-induced behaviors. Nat Neurosci 18:1094-100
Colangelo, Christopher M; Ivosev, Gordana; Chung, Lisa et al. (2015) Development of a highly automated and multiplexed targeted proteome pipeline and assay for 112 rat brain synaptic proteins. Proteomics 15:1202-14

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