中脑边缘系统的突触可塑性：物质滥用的治疗意义。
Synaptic plasticity in the mesolimbic system: therapeutic implications for substance abuse.
机构信息
Ernest Gallo Clinic and Research Center, University of California, San Francisco, California, USA.
出版信息
Ann N Y Acad Sci. 2010 Feb;1187:129-39. doi: 10.1111/j.1749-6632.2009.05154.x.
Abstract
In an ever-changing environment, animals must learn new behavioral strategies for the successful procurement of food, sex, and other needs. Synaptic plasticity within the mesolimbic system, a key reward circuit, affords an animal the ability to adapt and perform essential goal-directed behaviors. Ironically, drugs of abuse can also induce synaptic changes within the mesolimbic system, and such changes are hypothesized to promote deleterious drug-seeking behaviors in lieu of healthy, adaptive behaviors. In this review, we will discuss drug-induced neuroadaptations in excitatory transmission in the ventral tegmental area and the nucleus accumbens, two critical regions of the mesolimbic system, and the possible role of dopamine receptors in the development of these neuroadaptations. In particular, we will focus our discussion on recent studies showing changes in AMPA receptor function as a common molecular target of addictive drugs, and the possible behavioral consequences of such neuroadaptations.
摘要
在不断变化的环境中，动物必须学习新的行为策略，以成功获取食物、性和其他需求。中脑边缘系统内的突触可塑性是关键的奖励回路，使动物能够适应并执行重要的目标导向行为。具有讽刺意味的是，滥用药物也会在中脑边缘系统内诱导突触变化，并且这些变化被假设会促进有害的觅药行为，而不是健康、适应性的行为。在这篇综述中，我们将讨论腹侧被盖区和伏隔核中兴奋性传递的药物诱导神经适应性，这两个是中脑边缘系统的关键区域，以及多巴胺受体在这些神经适应性发展中的可能作用。特别是，我们将重点讨论最近的研究，这些研究表明 AMPA 受体功能的变化是成瘾药物的共同分子靶点，以及这种神经适应性的可能行为后果。
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Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4894-9. doi: 10.1073/pnas.0811507106. Epub 2009 Mar 4.
2
Behavioral sensitization to amphetamine is not accompanied by changes in glutamate receptor surface expression in the rat nucleus accumbens.对苯丙胺的行为敏化并不伴随着大鼠伏隔核中谷氨酸受体表面表达的变化。
J Neurochem. 2009 Apr;109(1):35-51. doi: 10.1111/j.1471-4159.2009.05911.x. Epub 2009 Jan 22.
3
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Nat Neurosci. 2009 Feb;12(2):182-9. doi: 10.1038/nn.2250. Epub 2009 Jan 11.
4
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5
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6
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Biochem Biophys Res Commun. 2009 Jan 30;379(1):65-9. doi: 10.1016/j.bbrc.2008.12.003. Epub 2008 Dec 12.
7
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10
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