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