The study by Ducret et al. (
1) in this issue of Biological Psychiatry is an important contribution to our understanding of the impact of glial glutamate transport restoration in addiction-related behaviors and offers insight into treatment of substance use disorders (SUDs) using N-acetylcysteine (NAC). Specifically, the authors found that NAC restored expression of the glial glutamate transporter (GLT-1), as well as increased sensitivity to punishment in animals given extended access to cocaine self-administration. Of note, the typical reduction in nucleus accumbens core GLT-1 after self-administered cocaine was found after “self-imposed abstinence” from cocaine in this study, rather than after experimenter-induced withdrawal, and this effect was access dependent. A reduction in GLT-1 also was found in the dorsolateral striatum. The NAC treatment regimen used to restore GLT-1 and reduce cocaine-related behaviors in this study was chronic (administered over the course of 23 sessions), and the dose used was lower (60 mg/kg) than that of some other preclinical studies [e.g., 100 mg/kg (
- Ducret E.
- Puaud M.
- Lacoste J.
- Belin-Rauscent A.
- Fouyssac M.
- Dugast E.
- et al.
N-acetylcysteine facilitates self-imposed abstinence after escalation of cocaine intake.
Biol Psychiatry. 2016; 8: 226-234
2)], perhaps leading to biological levels more akin those that found in humans, given the poor bioavailability of NAC (
- Reissner K.J.
- Gipson C.D.
- Tran P.K.
- Knackstedt L.A.
- Scofield M.D.
- Kalivas P.W.
Glutamate transporter GLT-1 mediates N-acetylcysteine inhibition of cocaine reinstatement.
Addict Biol. 2015; 20: 316-323
3). The authors conclude that NAC aids in restoration of control over intake of cocaine after it is paired with a negative consequence (foot shock) by aiding in glutamatergic reorganization. Given the shift from ventral to dorsal striatum that has been found to underlie the development of compulsive drug seeking, the logical progression from the conclusions of this study is that NAC treatment may aid in the reversal of this shift to allow control over drug seeking to be re-established.
- McClure E.A.
- Gipson C.D.
- Malcolm R.J.
- Kalivas P.W.
- Gray K.M.
Potential role of N-acetylcysteine in the management of substance use disorders.
CNS Drugs. 2014; 28: 95-106
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- N-acetylcysteine facilitates self-imposed abstinence after escalation of cocaine intake.Biol Psychiatry. 2016; 8: 226-234
- Glutamate transporter GLT-1 mediates N-acetylcysteine inhibition of cocaine reinstatement.Addict Biol. 2015; 20: 316-323
- Potential role of N-acetylcysteine in the management of substance use disorders.CNS Drugs. 2014; 28: 95-106
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Published online: May 18, 2016
Accepted: May 11, 2016
Received in revised form: May 11, 2016
Received: March 10, 2016
© 2016 Society of Biological Psychiatry.
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- N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine IntakeBiological PsychiatryVol. 80Issue 3Open Access