ArticleTranslational psychiatry2026
A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse.
Article in Translational psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cocaine addiction is characterized by high relapse rates associated with glutamate dysregulation, presenting significant challenges for long-term treatment. N-acetylcysteine (NAC) has shown promise in preventing drug relapse by normalizing glutamate function, potentially mediated by glutamate 2/3 (mGlu2/3) receptor activation. This study investigated the therapeutic potential of NAC in reducing cocaine-seeking behavior using the self-administration model. After establishing stable cocaine self-administration and a 7-day abstinence period, rats received a single dose of NAC (100 mg/kg, i.p.) 30 min before the first extinction training session. NAC significantly reduced cocaine-seeking behavior on the first day of extinction but not in subsequent extinction sessions. Following extinction, tests for cue-induced reinstatement and spontaneous recovery were conducted. Results showed that NAC administration on the first day of extinction effectively reduced cocaine-seeking during the reinstatement test, with effects lasting at least 28 days. The mGlu2/3 antagonist LY341495 (1 mg/kg) fully blocked this enduring suppression of reinstatement without altering the immediate decrease in drug-seeking observed on the first day of extinction. Additionally, NAC administration on the initial extinction day also reduced context-induced reinstatement of cocaine-seeking behavior. These results indicate that NAC exerts its anti-relapse effects via mGlu2/3 receptors. A single NAC treatment combined with extinction training can produce lasting suppression of relapse, highlighting its therapeutic promise for addiction treatment.
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