(provided by candidate): The number of genes that mediate the process of addiction is large numbering possibly in the hundreds. One of the purposes of research into addiction is to find novel components that mediate addiction and which may be targeted for therapy. We have taken an unbiased classical genetic approach to find genes that control one aspect of addiction, sensitization to the drug. Using forward genetic screen we have isolated several mutants that are hyper or hypo-sensitive to cocaine in a locomotor response assay. One of these mutants, Gridlock'd, has low response to cocaine and amphetamine. We have mapped the mutation to chromosome 8. I propose to fine map this mutation on chromosome 8 (Objective 1), clone the mutation (Objective2) and behaviorally characterize the mutation (Objective 3). The cloning of Gridlock'd could reveal a new component of the incentive motivational reward pathway that leads to addiction. The knowledge of this new component could lead to therapies designed to target this pathway.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA024556-04
Application #
7770837
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2008-03-01
Project End
2011-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
4
Fiscal Year
2010
Total Cost
$57,686
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Neurosciences
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Kumar, Vivek; Kim, Kyungin; Joseph, Chryshanthi et al. (2013) C57BL/6N mutation in cytoplasmic FMRP interacting protein 2 regulates cocaine response. Science 342:1508-12
Yoo, Seung-Hee; Mohawk, Jennifer A; Siepka, Sandra M et al. (2013) Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Cell 152:1091-105
Geyfman, Mikhail; Kumar, Vivek; Liu, Qiang et al. (2012) Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis. Proc Natl Acad Sci U S A 109:11758-63
Koike, Nobuya; Yoo, Seung-Hee; Huang, Hung-Chung et al. (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338:349-54
Kumar, Vivek; Kim, Kyungin; Joseph, Chryshanthi et al. (2011) Second-generation high-throughput forward genetic screen in mice to isolate subtle behavioral mutants. Proc Natl Acad Sci U S A 108 Suppl 3:15557-64
Lin, Kevin K; Kumar, Vivek; Geyfman, Mikhail et al. (2009) Circadian clock genes contribute to the regulation of hair follicle cycling. PLoS Genet 5:e1000573
Takahashi, Joseph S; Shimomura, Kazuhiro; Kumar, Vivek (2008) Searching for genes underlying behavior: lessons from circadian rhythms. Science 322:909-12