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The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis.
Pharmacological Reviews ( IF 21.1 ) Pub Date : 2016-07-01 , DOI: 10.1124/pr.116.012484
M D Scofield 1 , J A Heinsbroek 2 , C D Gipson 2 , Y M Kupchik 2 , S Spencer 2 , A C W Smith 2 , D Roberts-Wolfe 2 , P W Kalivas 2
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The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances.

中文翻译:

伏隔核:跨药物类别的成瘾机制反映了谷氨酸稳态的重要性。

伏伏核是基底神经节的主要输入结构,它整合了来自皮质和边缘结构的信息,以介导目标导向的行为。长期接触几种滥用药物会破坏该地区的可塑性,从而使与毒品有关的线索产生寻求毒品的病理动机。从慢性药物暴露中退出后,伏隔核内发生了谷氨酸能传递的许多改变。这些药物诱导的神经适应充当复发易感性的分子基础。在这篇综述中,我们重点研究伏隔核中谷氨酸信号转导在成瘾相关行为中的作用。首先,我们探索伏隔核,包括存在的细胞类型和神经元种群以及传入和传出的连接。接下来,我们讨论啮齿动物成瘾模型,并评估这些模型用于测试候选药物疗法以预防复发的可行性。然后,我们提供了一篇文献综述,描述了滥用和停药后伏隔中突触可塑性如何改变,以及伏隔中谷氨酸系统的药理处理如何在实验室环境中抑制药物寻找。最后,我们检查了来自临床试验的结果,在这些试验中,旨在操纵谷氨酸系统的药物疗法已有效治疗人类患者的复发。进一步阐明滥用药物如何改变伏隔内的谷氨酸能可塑性,对于开发用于治疗所有成瘾性物质上瘾的新疗法的发展将是必要的。
更新日期:2019-11-01
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