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

被引:0
作者
Shelley L Amen
Linda B Piacentine
Muhammad E Ahmad
Shi-Jiang Li
John R Mantsch
Robert C Risinger
David A Baker
机构
[1] Medical College of Wisconsin,Department of Pharmacology and Toxicology
[2] Medical College of Wisconsin,Department of Psychiatry and Behavioral Medicine
[3] Medical College of Wisconsin,Department of Biophysics
[4] Marquette University,Department of Biomedical Sciences
来源
Neuropsychopharmacology | 2011年 / 36卷
关键词
-acetyl cysteine; cocaine; drug abuse; craving; reinstatement; cystine–glutamate exchange;
D O I
暂无
中图分类号
学科分类号
摘要
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 xc– 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.
引用
收藏
页码:871 / 878
页数:7
相关论文
共 115 条
  • [61] Saladin M(undefined)undefined undefined undefined undefined-undefined
  • [62] McRae A(undefined)undefined undefined undefined undefined-undefined
  • [63] Li SJ(undefined)undefined undefined undefined undefined-undefined
  • [64] Biswal B(undefined)undefined undefined undefined undefined-undefined
  • [65] Li Z(undefined)undefined undefined undefined undefined-undefined
  • [66] Risinger R(undefined)undefined undefined undefined undefined-undefined
  • [67] Rainey C(undefined)undefined undefined undefined undefined-undefined
  • [68] Cho JK(undefined)undefined undefined undefined undefined-undefined
  • [69] Li X(undefined)undefined undefined undefined undefined-undefined
  • [70] Li J(undefined)undefined undefined undefined undefined-undefined