Using functional MRI, N-acetyl cysteine (NAC, cysteine prodrug) and baclofen (BLF, gamma-amino-butyric acid (GABA) receptor agonist), will be evaluated in regards to reinstatement of cocaine behavior in rat and craving behavior in human. This proposal seeks to develop the preclinical findings that the cystine/glutamate antiporter may restore basal (non-drug) tone of glutamate surrounding neurons in drug reward-associated regions of the brain, which may then reduce craving behavior. NAC and BLF will be administered 1) to rats during the extinction phase of a self-administration reinstatement paradigm and 2) to human cocaine dependent subjects during a period of abstinence. A 3T fMRI scanner will be used for human studies and 9.4T and 3T scanners for rodent studies with BOLD signal and perfusion imaging to describe functional changes in drug-related neural regions. The anticipated attenuation of craving and high (in humans) and reinstatement (in rats) will be correlated with the neuronal effects of cocaine and each pharmacologic agent at varying doses. This study will contribute to a better understanding of the neural mechanisms underlying cocaine addiction and may therefore lead to targeted pharmacotherapy for those struggling with cocaine's potent craving and relapse phenomenology.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA019754-03
Application #
7409053
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2006-04-01
Project End
2009-07-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2008
Total Cost
$33,321
Indirect Cost
Name
Medical College of Wisconsin
Department
Pharmacology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Amen, Shelley L; Piacentine, Linda B; Ahmad, Muhammad E et al. (2011) Repeated N-acetyl cysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology 36:871-8