N-Acetylcysteine reverses cocaine-induced metaplasticity.
N-Acetylcysteine reverses cocaine-induced metaplasticity.
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DOI：
10.1038/nn.2250
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发表时间：
2009-02
影响因子：
25
通讯作者：
Kalivas, Peter W.
中科院分区：
文献类型：
--
作者：
Moussawi, Khaled;Pacchioni, Alejandra;Moran, Megan;Olive, M. Foster;Gass, Justin T.;Lavin, Antonieta;Kalivas, Peter W.
可卡因成瘾的特征是发展适应性行为的能力受损，这种能力可以与可卡因寻求竞争，这意味着在对调节动机性行为至关重要的皮质类固醇回路中诱导可塑性的能力不足。我们发现，从可卡因自我管理撤回大鼠有一个显着的在体内缺陷的能力，发展长时程电位（LTP）和抑郁症（LTD）的核心亚区后，前额叶皮层的刺激。N-乙酰半胱氨酸治疗通过激活胱氨酸-谷氨酸交换从而刺激突触外代谢型谷氨酸受体（mGluR）来防止动物模型中的复发和人类中的渴望。N-乙酰半胱氨酸处理恢复的能力，诱导LTP和LTD的间接刺激mGluR 2/3和mGluR 5，分别。皮质醇自身给药诱导后可塑性，抑制突触可塑性的进一步诱导，这种损害可以通过N-乙酰半胱氨酸逆转，N-乙酰半胱氨酸是一种也可以防止复发的药物。
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 critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefrontal cortex. N-acetylcysteine treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). N-acetylcysteine treatment restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Cocaine self-administration induces metaplasticity that inhibits the further induction of synaptic plasticity, and this impairment can be reversed by N-acetylcysteine, a drug that also prevents relapse.
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