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

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 2400mg/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 60mg). 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 0mg 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.

Keywords: Attentional bias; Cocaine; Human; Pharmacotherapy; Self-administration; n-Acetylcysteine.

Conflict of interest statement

Conflict of Interest

The authors declare no real or potential conflicts of interest relevant to this research.

Copyright © 2017 Elsevier B.V. All rights reserved.

Figures

Figure 1

Mean difference in reaction time in milliseconds (± SEM) during placebo (PLB; open bars) and n-acetylcysteine (nAC; filled bars) as a function of intranasal cocaine dose (0, 30, and 60 mg) from the Visual-Probe Task. Data represent the mean difference score (Cocaine - Neutral) for thirteen individuals (N = 13). An asterisk (*) indicates a significant difference between placebo and n-acetylcysteine maintenance (p < 0.05).

Figure 2

Mean number of drug choices (± SEM) as a function of intranasal cocaine dose (0, 30, and 60 mg) from the Drug Choice Procedure under placebo (open circles) or n-acetylcysteine (open squares) maintenance. Data on the left represent participants who were maintained on placebo first (n = 7) and data on the right correspond with those who received n-acetylcysteine first (n = 7). Filled symbols indicate a significant within-group difference from 0 mg cocaine during placebo maintenance (p < 0.05). An asterisk (*) indicates a significant difference between participants maintained on placebo or n-acetylcysteine first at a given dose of n-acetylcysteine and cocaine.

Figure 3

Mean peak subject rating (± SEM) as a function of intranasal cocaine dose (0, 30, and 60 mg) from the Drug-Effect Questionnaire under placebo (PLB; open circles) or n-acetylcysteine (nAC; open squares) maintenance. Filled symbols indicate a significant difference from 0 mg cocaine during placebo maintenance (p < 0.05). An asterisk (*) indicates a significant difference between n-acetylcysteine maintenance conditions at a given dose of cocaine (p < 0.05).

Figure 4

Mean peak effect (± SEM) for systolic blood pressure, diastolic blood pressure, and heart rate as a function of intranasal cocaine dose (0, 30, and 60 mg) during placebo (PLB; open circles) and n-acetylcysteine (nAC; open squares) maintenance. The remaining details are the same as those for Figure 3.