N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order

B. L. Bolin, Joseph L. Alcorn, Joshua A. Lile, Craig R. Rush, Abner O. Rayapati, Lon R. Hays, William W. Stoops

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. Methods The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400 mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60 mg). Fourteen individuals (N = 14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Results Cocaine-cue attentional bias was greatest following administration of 0 mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. Conclusions These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues.

Original languageEnglish
Pages (from-to)452-460
Number of pages9
JournalDrug and Alcohol Dependence
Volume178
DOIs
StatePublished - Sep 1 2017

Bibliographical note

Funding Information:
This research was supported by grants from the National Institute on Drug Abuse [R21 DA035376; T32 DA035200] and National Center for Advancing Translational Sciences [UL1 TR000117] of the National Institutes of Health. This funding agency had no role in study design, data collection or analysis, or preparation and submission of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

  • Attentional bias
  • Cocaine
  • Human
  • Pharmacotherapy
  • Self-administration
  • n-Acetylcysteine

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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