Article abstract
Nature Neuroscience 12, 182 - 189 (2009)
Published online: 11 January 2009 | doi:10.1038/nn.2250
N-Acetylcysteine reverses cocaine-induced metaplasticity
Khaled Moussawi1, Alejandra Pacchioni1, Megan Moran1, M Foster Olive2, Justin T Gass2, Antonieta Lavin1 & Peter W Kalivas1
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 We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the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.
- Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue BSB410, Charleston, South Carolina, USA
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 173 Ashley Avenue BSB410, Charleston, South Carolina, USA
Correspondence to: Peter W Kalivas1 e-mail: kalivasp@musc.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
A role for BDNF in cocaine reward and relapseNature Neuroscience News and Views (01 Aug 2007)
Unmet expectations: The brain mindsNature Medicine News and Views (01 Jan 2003)
RESEARCH
Neuroadaptations in cystine-glutamate exchange underlie cocaine relapseNature Neuroscience Article (01 Jul 2003)
Cocaine Self-Administration Reduces Excitatory Responses in the Mouse Nucleus Accumbens ShellNeuropsychopharmacology Original Article
See all 75 matches for Research
