N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake
N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake
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DOI：
10.1016/j.biopsych.2015.09.019
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发表时间：
2016-08-01
影响因子：
10.6
通讯作者：
Belin, David
中科院分区：
文献类型：
--
作者：
Ducret, Eric;Puaud, Mickael;Belin, David
BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown.METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation. Rats then received daily saline or NAC (60 mg/kg, intraperitoneal) treatment and were tested under a progressive ratio and several consecutive sessions in which lever presses were punished by mild electric foot shocks.RESULTS: NAC increased the sensitivity to punishment in LgA rats only, thereby promoting abstinence. Following the cessation of punishment, NAC-treated LgA rats failed to recover fully their prepunishment cocaine intake levels and resumed cocaine SA at a lower rate than short access and vehicle-treated LgA rats. However, NAC altered neither the escalation of SA nor the motivation for cocaine. At the neurobiological level, NAC reversed cocaine-induced decreases in the glutamate type 1 transporter observed in both the nucleus accumbens and the dorsolateral striatum. NAC also increased the expression of Zif268 in the nucleus accumbens and dorsolateral striatum of LgA rats.CONCLUSIONS: Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.
