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.
| 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 |
