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.
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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.
Refer to Web version on PubMed Central for supplementary material.
Bolin, B. Levi; Alcorn, Joseph L. III; Lile, Joshua A.; Rush, Craig R.; Rayapati, Abner O.; Hays, Lon R.; and Stoops, William W., "N-Acetylcysteine Reduces Cocaine-Cue Attentional Bias and Differentially Alters Cocaine Self-Administration Based on Dosing Order" (2017). Behavioral Science Faculty Publications. 39.