Repeated N-acetyl cysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology 2011 Mar;36(4):871-8
Date
12/17/2010Pubmed ID
21160464Pubmed Central ID
PMC3052624DOI
10.1038/npp.2010.226Scopus ID
2-s2.0-79951508231 (requires institutional sign-in at Scopus site) 125 CitationsAbstract
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 DAAuthors
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinLinda 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
AcetylcysteineAdult
Animals
Behavior, Addictive
Cocaine-Related Disorders
Conditioning, Operant
Humans
Male
Middle Aged
Rats
Rats, Sprague-Dawley
Species Specificity