CART peptides are neurochemical messengers in the brain that are involved in drug addiction, and they may be especially relevant to psychostimulants like cocaine and methamphetamine. Indeed, administration of cocaine or amphetamine to animals results in rapid upregulation of CART mRNA. Also, when CART peptides are injected into the brain, the animals behave as though they have been given psychostimulants. Locomotor activity increases and they produce signs of being dependent. Because CART peptides are naturally occurring mediators and modulators of these drugs, and because they may make good targets for new medications, they must be well understood. This proposal focuses on the brain mechanisms that control the levels of these peptides. In particular, the research will produce an understanding of how the CART gene is regulated by cellular events such as stimulation by drug and signal transduction pathways. The CART gene """"""""promoter,"""""""" which regulates expression of the gene and ultimately the level of its peptide product, will be characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015162-03
Application #
6743779
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (01))
Program Officer
Satterlee, John S
Project Start
2002-05-01
Project End
2007-03-31
Budget Start
2004-04-01
Budget End
2007-03-31
Support Year
3
Fiscal Year
2004
Total Cost
$240,000
Indirect Cost
Name
Emory University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Job, Martin O; Perry, Joanna; Shen, Li L et al. (2014) Cocaine-and-Amphetamine Regulated Transcript (CART) peptide attenuates dopamine- and cocaine-mediated locomotor activity in both male and female rats: lack of sex differences. Neuropeptides 48:75-81
Kuhar, Michael J; Cross, Dorthie (2013) Collegial ethics: supporting our colleagues. Sci Eng Ethics 19:677-84
Job, Martin O; Shen, Li L; Kuhar, Michael J (2013) The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration. Neurosci Lett 550:179-83
Job, Martin O; Kuhar, Michael J (2012) Intraperitoneal Administration of CART 55-102 Inhibits Psychostimulant-Induced Locomotion. J Drug Alcohol Res 1:
Job, M O; Licata, J; Hubert, G W et al. (2012) Intra-accumbal administration of shRNAs against CART peptides cause increases in body weight and cocaine-induced locomotor activity in rats. Brain Res 1482:47-54
Kuhar, Michael J (2011) Collegial ethics: what, why and how. Drug Alcohol Depend 119:235-8
Moffett, Mark C; Song, Jane; Kuhar, Michael J (2011) CART peptide inhibits locomotor activity induced by simultaneous stimulation of D1 and D2 receptors, but not by stimulation of individual dopamine receptors. Synapse 65:1-7
Lin, Yiming; Hall, Randy A; Kuhar, Michael J (2011) CART peptide stimulation of G protein-mediated signaling in differentiated PC12 cells: identification of PACAP 6-38 as a CART receptor antagonist. Neuropeptides 45:351-8
Kuhar, Michael J (2010) Measuring levels of proteins by various technologies: can we learn more by measuring turnover? Biochem Pharmacol 79:665-8
Rogge, George A; Shen, Li-Ling; Kuhar, Michael J (2010) Chromatin immunoprecipitation assays revealed CREB and serine 133 phospho-CREB binding to the CART gene proximal promoter. Brain Res 1344:1-12

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