Elsevier

Biological Psychiatry

Volume 63, Issue 3, 1 February 2008, Pages 338-340
Biological Psychiatry

Brief Report
N-Acetylcysteine Reduces Extinction Responding and Induces Enduring Reductions in Cue- and Heroin-Induced Drug-Seeking

https://doi.org/10.1016/j.biopsych.2007.06.008Get rights and content

Background

Previous studies show that the acute administration of N-acetylcysteine (NAC) inhibits the desire for cocaine in addicts and cocaine-seeking in animals.

Methods

Rats were trained to self-administer heroin, and the reinstatement model of drug seeking was used to determine whether chronic NAC treatment inhibited heroin-seeking.

Results

Daily NAC administration inhibited cue- and heroin-induced seeking. Moreover, repeated NAC administration during extinction training reduced extinction-responding and inhibited cue- and heroin-induced reinstatement for up to 40 days after discontinuing daily NAC injection.

Conclusions

These data show that daily NAC inhibits heroin-induced reinstatement and produces an enduring reduction in cue- and heroin-induced drug seeking for over 1 month after the last injection of NAC. Both the inhibitory effect of NAC on the reinstatement of heroin-seeking and the ability of NAC to reduce extinction-responding support clinical evaluation of repeated NAC administration to decrease in drug-seeking in heroin addicts.

Section snippets

Methods and Materials

Detailed methods are provided in Supplement 1. Male Sprague-Dawley rats were housed individually on a reversed 12-hour/12-hour light-dark cycle. All experiments were conducted during the dark period according to specifications of the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Rats were anesthetized with ketamine hydrochloric acid (87.5 mg/kg, IP) and xylazine (5 mg/kg, IP) and implanted with indwelling jugular catheters as described previously (6). Heroin

Results

After training to self-administer heroin, animals were placed into daily NAC (n = 24) or vehicle (n = 23) treatment groups to begin extinction training. The average number of active lever presses over the last 3 days of self-administration training was equal among the groups (NAC = 62 ± 17; vehicle = 58 ± 14, mean ± SEM). Figure 1A illustrates that NAC (100 mg/kg, IP) significantly augmented the extinction of active lever pressing compared with vehicle pretreated subjects; an effect most

Discussion

These data show that, akin to the effects of acute NAC pretreatment in animals trained to self-administer cocaine (3, 4), chronic pretreatment with NAC inhibits cue- and heroin-induced drug-seeking in the reinstatement model of relapse. Given the recent clinical trial showing that NAC was successful in reducing cue-induced drug desire in cocaine addicts (5), these data pose the possibility that NAC might also be successful in a similar trial in heroin addicts. Perhaps more significant is the

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