Hundreds of publications have shown the importance of CART peptides. They modulate drugs of abuse, regulate food intake and have other physiologic roles. In order for CART peptides to carry out these functions, they must be regulated. In other words, the levels of the peptides must be able to change fairly rapidly in order to respond to their needs and demands. Indeed, it has been shown that CART levels do change quickly (in hours) in response to cocaine and amphetamine and food deprivation, for example. This project will study how CART levels change, or in other words, the mechanisms accounting for the changes. This is essential knowledge for a full understanding of these important peptides. This work will focus on CART in drug abuse, and on the regulation of the CART expression by cell signaling and by control of the promoter of the CART gene. Many of the experiments will be carried out in brain which is the most relevant tissue for the functions considered. More specifically, much work will study CART expression and regulation in the nucleus accumbens which is a key center for understanding drug addiction. It is expected that a critical role for CREB, a known regulator in drug addiction, will be established for CART regulation. In addition, other molecules like CREB transcription factors, will be identified that also play a role in regulating CART. Finally, the role of calcium, an important intracellular regulator will be shown to regulate CART as well. All of these regulatory factors act together and integrate in the intact animal and the behavioral effects of some experimental changes will be examined as well. It is expected that altering CART regulation will in turn alter the effects of some drugs such as cocaine, for example. Understanding how CART levels are controlled may lead to new strategies to develop medications that affect the CART system. Such medications could very well be helpful for public health problems such as drug addiction and obesity. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015162-05
Application #
7503408
Study Section
Molecular Neuropharmacology and Signaling Study Section (MNPS)
Program Officer
Koustova, Elena
Project Start
2002-05-01
Project End
2011-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
5
Fiscal Year
2008
Total Cost
$362,270
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
Keating, Glenda L; Kuhar, Michael J; Bliwise, Donald L et al. (2010) Wake promoting effects of cocaine and amphetamine-regulated transcript (CART). Neuropeptides 44:241-6
Hubert, G W; Manvich, D F; Kuhar, M J (2010) Cocaine and amphetamine-regulated transcript-containing neurons in the nucleus accumbens project to the ventral pallidum in the rat and may inhibit cocaine-induced locomotion. Neuroscience 165:179-87

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