ArticlePsychopharmacology2016
N-acetylcysteine amide (AD4) reduces cocaine-induced reinstatement.
Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse.Translational psychiatry · 2026Article
- Thiol-Based Redox Molecules: Potential Antidotes for Acrylamide Toxicity.Antioxidants (Basel, Switzerland) · 2024Article
- Exploring the potential link between ΔFosB andActa neuropsychiatrica · 2024Review
- Neuroimmune modulators as novel pharmacotherapies for substance use disorders.Brain, behavior, & immunity - health · 2024Article
- Rheumatoid Arthritis and Reactive Oxygen Species: A Review.Current issues in molecular biology · 2023Article
- Evaluation of the 5-HTPharmacological reports : PR · 2023Article
- N-acetylcysteine in substance use disorder: a lesson from preclinical and clinical research.Pharmacological reports : PR · 2021Review
- Review
- Effects of chronic cocaine self-administration and N-acetylcysteine on learning, cognitive flexibility, and reinstatement in nonhuman primates.Psychopharmacology · 2019Article
- Drug addiction: a curable mental disorder?Acta pharmacologica Sinica · 2018Review
- Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse.The international journal of neuropsychopharmacology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleChronic exposure to drugs of abuse changes glutamatergic transmission in human addicts and animal models. N-acetylcysteine (NAC) is a cysteine prodrug that indirectly activates cysteine-glutamate antiporters. In the extrasynaptic space, NAC restores basal glutamate levels during drug abstinence and normalizes increased glutamatergic tone in rats during reinstatement to drugs of abuse. In initial clinical trials, repeated NAC administration seems to be promising for reduced craving in cocaine addicts.
objectiveIn this study, NAC-amide, called AD4 or NACA, was examined in intravenous cocaine self-administration and extinction/reinstatement procedures in rats. We investigated the behavioral effects of AD4 in the olfactory bulbectomized (OBX) rats, considered an animal model of depression. Finally, we tested rats injected with AD4 or NAC during 10-daily extinction training sessions to examine subsequent cocaine seeking.
resultsAD4 (25-75 mg kg(-1)) given acutely did not alter the rewarding effects of cocaine in OBX rats and sham-operated controls. However, at 6.25-50 mg kg(-1), AD4 decreased dose-dependently cocaine seeking and relapse triggered by cocaine priming or drug-associated conditioned cues in both phenotypes. Furthermore, repeated treatment with AD4 (25 mg kg(-1)) or NAC (100 mg kg(-1)) during daily extinction trials reduced reinstatement of drug-seeking behavior in sham-operated controls. In the OBX rats only, AD4 effectively blocked cocaine-seeking behavior.
conclusionsOur results demonstrate that AD4 is effective at blocking cocaine-seeking behavior, highlighting its potential clinical use toward cocaine use disorder.
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