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Repeated N-acetyl cysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology 2011 Mar;36(4):871-8

Date

12/17/2010

Pubmed ID

21160464

Pubmed Central ID

PMC3052624

DOI

10.1038/npp.2010.226

Scopus ID

2-s2.0-79951508231   107 Citations

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.

Author List

Amen SL, Piacentine LB, Ahmad ME, Li SJ, Mantsch JR, Risinger RC, Baker DA

Authors

Shi-Jiang Li PhD Professor in the Biophysics department at Medical College of Wisconsin
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Linda Piacentine BS,MS,NP,PhD Assistant Professor in the College of Nursing department at Marquette University




MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Adult
Animals
Behavior, Addictive
Cocaine-Related Disorders
Conditioning, Operant
Humans
Male
Middle Aged
Rats
Rats, Sprague-Dawley
Species Specificity