N-Acetylcysteine reverses cocaine-induced metaplasticity

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

Research output: Contribution to journalArticlepeer-review

340 Scopus citations


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 We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the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
Issue number2
StatePublished - Feb 2009
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)


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