N-Acetylcysteine reverses cocaine-induced metaplasticity
Autor: | Antonieta Lavin, Alejandra M. Pacchioni, Justin T. Gass, Peter W. Kalivas, Khaled Moussawi, M. Foster Olive, Megan M. Moran |
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Rok vydání: | 2009 |
Předmět: |
Male
Pyridines Receptor Metabotropic Glutamate 5 Long-Term Potentiation Prefrontal Cortex Self Administration Nucleus accumbens Receptors Metabotropic Glutamate Article Nucleus Accumbens Rats Sprague-Dawley Cocaine-Related Disorders Metaplasticity Secondary Prevention Animals Long-Term Synaptic Depression Neuronal Plasticity Behavior Animal Metabotropic glutamate receptor 5 General Neuroscience Excitatory Postsynaptic Potentials Long-term potentiation Free Radical Scavengers Acetylcysteine Rats Substance Withdrawal Syndrome Disease Models Animal nervous system Metabotropic glutamate receptor Synaptic plasticity Metabotropic glutamate receptor 2 Psychology Excitatory Amino Acid Antagonists Neuroscience |
Zdroj: | Nature neuroscience |
ISSN: | 1546-1726 1097-6256 |
Popis: | 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 We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the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. |
Databáze: | OpenAIRE |
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