This is an application for a NIDA Research Scientist Award. A program of research is proposed that focuses on psychostimulant drugs but has implications for other drugs of abuse. The three general areas funded by NIDA that will be explored are as follows. 1. Medications development. A group of unique phenyltropane compounds will be characterized so that several candidates for substitute medications can be identified. The compounds will be screened in behavioral assays in rodents and nonhuman primates so as to find compounds that are active in vivo, not overtly toxic, potent and long-acting, effective in reducing cocaine self- administration, and have a low abuse liability. 2. Mechanisms controlling synthesis and degradation of transporters. Dopamine and serotonin transporters are targets or """"""""receptors"""""""" for drugs of abuse as well as for many therapeutically useful drugs. Since the levels of these proteins are dependent on a balance between synthesis and degradation, and because factors controlling levels need to be understood, methods for determining these factors will be developed and refined. 3. Physiology of CART peptides. CART peptides are novel neuropeptides that are highly concentrated in areas of the brain implicated in mechanisms of drug abuse. These areas include the nucleus accumbens, ventral pallidum, amygdala and midbrain ventral tegmentum. Preliminary data show that these peptides have physiologic effects. Their precise role in the mechanisms of action of drugs of abuse will be examined. An interdisciplinary team will focus on these problems. Several predoc as well as post doctoral fellows will be trained during this work.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA000418-05
Application #
6634133
Study Section
Special Emphasis Panel (ZDA1-MXS-M (12))
Program Officer
Patel, Amrat
Project Start
1999-04-15
Project End
2004-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
5
Fiscal Year
2003
Total Cost
$120,463
Indirect Cost
Name
Emory University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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
Rogge, George A; Jones, Douglas C; Green, Thomas et al. (2009) Regulation of CART peptide expression by CREB in the rat nucleus accumbens in vivo. Brain Res 1251:42-52
Kuhar, Michael J (2009) Blacklisting among scientists. Synapse 63:539-40
Lima, F B; Henderson, J A; Reddy, A P et al. (2008) Unique responses of midbrain CART neurons in macaques to ovarian steroids. Brain Res 1227:76-88
Francis, D D; Kuhar, M J (2008) Frequency of maternal licking and grooming correlates negatively with vulnerability to cocaine and alcohol use in rats. Pharmacol Biochem Behav 90:497-500
Jaworski, Jason N; Hansen, Stephen T; Kuhar, Michael J et al. (2008) Injection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens reduces cocaine self-administration in rats. Behav Brain Res 191:266-71
Moffett, M C; Vicentic, A; Kozel, Marie et al. (2007) Maternal separation alters drug intake patterns in adulthood in rats. Biochem Pharmacol 73:321-30
Jaworski, Jason N; Kimmel, Heather L; Mitrano, Darlene A et al. (2007) Intra-VTA CART 55-102 reduces the locomotor effect of systemic cocaine in rats: an isobolographic analysis. Neuropeptides 41:65-72