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 (
2
)], perhaps leading to biological levels more akin those that found in humans, given
the poor bioavailability of NAC (
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.To read this article in full you will need to make a payment
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References
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- A minireview on N-acetylcysteine: An old drug with new approaches.Life Sci. 2016; 151: 363
- N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking.Biol Psychiatry. 2008; 63: 338-340
- A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence.Am J Addict. 2013; 22: 443-452
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Article info
Publication history
Published online: May 18, 2016
Accepted:
May 11,
2016
Received in revised form:
May 11,
2016
Received:
March 10,
2016
Identification
Copyright
© 2016 Society of Biological Psychiatry.
ScienceDirect
Access this article on ScienceDirectLinked Article
- N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine IntakeBiological PsychiatryVol. 80Issue 3Open Access
