N-Acetylcysteine reverses cocaine-induced metaplasticity

Khaled Moussawi, Alejandra Pacchioni, Megan Moran, Michael Olive, Justin T. Gass, Antonieta Lavin, Peter W. Kalivas

Research output: Contribution to journalArticle

272 Citations (Scopus)

Abstract

Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

Original languageEnglish (US)
Pages (from-to)182-189
Number of pages8
JournalNature Neuroscience
Volume12
Issue number2
DOIs
StatePublished - Feb 2009
Externally publishedYes

Fingerprint

Aptitude
Acetylcysteine
Cocaine
Self Administration
Long-Term Potentiation
Depression
Recurrence
Cocaine-Related Disorders
Metabotropic Glutamate Receptors
Neuronal Plasticity
Cystine
Psychological Adaptation
Nucleus Accumbens
Prefrontal Cortex
Glutamic Acid
Animal Models
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Moussawi, K., Pacchioni, A., Moran, M., Olive, M., Gass, J. T., Lavin, A., & Kalivas, P. W. (2009). N-Acetylcysteine reverses cocaine-induced metaplasticity. Nature Neuroscience, 12(2), 182-189. https://doi.org/10.1038/nn.2250

N-Acetylcysteine reverses cocaine-induced metaplasticity. / Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, Michael; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W.

In: Nature Neuroscience, Vol. 12, No. 2, 02.2009, p. 182-189.

Research output: Contribution to journalArticle

Moussawi, K, Pacchioni, A, Moran, M, Olive, M, Gass, JT, Lavin, A & Kalivas, PW 2009, 'N-Acetylcysteine reverses cocaine-induced metaplasticity', Nature Neuroscience, vol. 12, no. 2, pp. 182-189. https://doi.org/10.1038/nn.2250
Moussawi K, Pacchioni A, Moran M, Olive M, Gass JT, Lavin A et al. N-Acetylcysteine reverses cocaine-induced metaplasticity. Nature Neuroscience. 2009 Feb;12(2):182-189. https://doi.org/10.1038/nn.2250
Moussawi, Khaled ; Pacchioni, Alejandra ; Moran, Megan ; Olive, Michael ; Gass, Justin T. ; Lavin, Antonieta ; Kalivas, Peter W. / N-Acetylcysteine reverses cocaine-induced metaplasticity. In: Nature Neuroscience. 2009 ; Vol. 12, No. 2. pp. 182-189.
@article{d6f92b9a569e43768e392cf9bac042d1,
title = "N-Acetylcysteine reverses cocaine-induced metaplasticity",
abstract = "Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.",
author = "Khaled Moussawi and Alejandra Pacchioni and Megan Moran and Michael Olive and Gass, {Justin T.} and Antonieta Lavin and Kalivas, {Peter W.}",
year = "2009",
month = "2",
doi = "10.1038/nn.2250",
language = "English (US)",
volume = "12",
pages = "182--189",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - N-Acetylcysteine reverses cocaine-induced metaplasticity

AU - Moussawi, Khaled

AU - Pacchioni, Alejandra

AU - Moran, Megan

AU - Olive, Michael

AU - Gass, Justin T.

AU - Lavin, Antonieta

AU - Kalivas, Peter W.

PY - 2009/2

Y1 - 2009/2

N2 - Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

AB - Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the nucleus accumbens core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.

UR - http://www.scopus.com/inward/record.url?scp=58849166971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58849166971&partnerID=8YFLogxK

U2 - 10.1038/nn.2250

DO - 10.1038/nn.2250

M3 - Article

C2 - 19136971

AN - SCOPUS:58849166971

VL - 12

SP - 182

EP - 189

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 2

ER -