Repeated N-Acetyl Cysteine Reduces Cocaine Seeking in Rodents and Craving in Cocaine-Dependent Humans

Authors

Shelley L. Amen, Medical College of Wisconsin
Linda B. Piacentine, Marquette UniversityFollow
Muhammad E. Ahmad, Medical College of Wisconsin
Shi-Jiang Li, Medical College of Wisconsin
John R. Mantsch, Marquette UniversityFollow
Robert C. Risinger, Medical College of Wisconsin
David A. Baker, Marquette UniversityFollow

Document Type

Article

Language

eng

Publication Date

3-2011

Publisher

Nature Publishing Group (Macmillan Publishers Limited)

Source Publication

Neuropsychopharmacology

Source ISSN

0893-133X

Original Item ID

DOI: 10.1038/npp.2010.226

Abstract

Addiction is a chronic relapsing disorder hypothesized to be produced by drug-induced plasticity that renders individuals vulnerable to craving-inducing stimuli such as re-exposure to the drug of abuse. Drug-induced plasticity that may result in the addiction phenotype includes increased excitatory signaling within corticostriatal pathways that correlates with craving in humans and is necessary for reinstatement in rodents. Reduced cystine–glutamate exchange by system x_c– appears to contribute to heightened excitatory signaling within the striatum, thereby posing this as a novel target in the treatment of addiction. In the present report, we examined the impact of repeated N-acetyl cysteine, which is commonly used to activate cystine–glutamate exchange, on reinstatement in rodents in a preclinical study and on craving in cocaine-dependent humans in a preliminary, proof-of-concept clinical experiment. Interestingly, repeated administration (7 days) of N-acetyl cysteine (60 mg/kg, IP) produced a significant reduction in cocaine (10 mg/kg, IP)-induced reinstatement, even though rats (N=10–12/group) were tested 24 h after the last administration of N-acetyl cysteine. The reduction in behavior despite the absence of the N-acetyl cysteine indicates that repeated N-acetyl cysteine may have altered drug-induced plasticity that underlies drug-seeking behavior. In parallel, our preliminary clinical data indicate that repeated administration (4 days) of N-acetyl cysteine (1200–2400 mg/day) to cocaine-dependent human subjects (N=4 per group) produced a significant reduction in craving following an experimenter-delivered IV injection of cocaine (20 mg/70 kg/60 s). Collectively, these data demonstrate that N-acetyl cysteine diminishes the motivational qualities of a cocaine challenge injection possibly by altering pathogenic drug-induced plasticity.

Comments

Accepted version. Neuropsychopharmacology, Vol. 36, No. 4 (March 2011): 871-878. DOI. © 2011 Nature Publishing Group (Macmillan Publishers Limited). Used with permission.

Recommended Citation

Amen, Shelley L.; Piacentine, Linda B.; Ahmad, Muhammad E.; Li, Shi-Jiang; Mantsch, John R.; Risinger, Robert C.; and Baker, David A., "Repeated N-Acetyl Cysteine Reduces Cocaine Seeking in Rodents and Craving in Cocaine-Dependent Humans" (2011). Biomedical Sciences Faculty Research and Publications. 145.
https://epublications.marquette.edu/biomedsci_fac/145