Biological substrates of addiction.
Biological substrates of addiction.
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DOI：
10.1002/wcs.1273
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发表时间：
2014-03
影响因子：
3.9
通讯作者：
Grueter, Brad A.
中科院分区：
文献类型：
--
作者：
Joffe, Max E.;Grueter, Carrie A.;Grueter, Brad A.
这篇综述介绍了成瘾、奖赏回路和实验室成瘾模型。成瘾是一种慢性疾病，其特征是强迫性药物寻求状态，尽管有负面后果，但仍然存在。成瘾研究的大多数进展都集中在滥用的经典和当代药物上，然而，对其他活动和刺激的成瘾也存在。滥用的物质有可能在行为、回路和突触层面引起大脑的长期变化。成瘾相关的行为变化涉及对药物寻求的启动，升级和痴迷，目前的研究主要集中在将这些表现映射到特定的神经通路上。众所周知，药物滥用会招募中脑边缘多巴胺系统的组成部分，包括延髓核和腹侧被盖区。此外，各种大脑区域的功能改变与药物滥用的具体表现密切相关。这些区域周边的mesolimbic途径可能发挥作用，在特定的观察到的合并症和内源性表型，可以促进，或引起的，药物滥用。突触结构、功能和连通性的改变以及表观遗传和遗传机制被认为是成瘾病理学的基础。在临床前模型中，在分子药理学和生物化学、离体和体内电生理学、放射学和行为学水平上研究这些持续变化。协调这些学科的研究工作并检查细胞类型和回路特异性现象是将临床前发现转化为有效治疗成瘾和相关疾病的可行医疗干预措施的关键组成部分。
This review is an introduction to addiction, the reward circuitry, and laboratory addiction models. Addiction is a chronic disease hallmarked by a state of compulsive drug seeking that persists despite negative consequences. Most of the advances in addiction research have centered on the canonical and contemporary drugs of abuse, however, addictions to other activities and stimuli also exist. Substances of abuse have the potential to induce long-lasting changes in the brain at the behavioral, circuit and synaptic levels. Addiction-related behavioral changes involve initiation, escalation and obsession to drug seeking and much of the current research is focused on mapping these manifestations to specific neural pathways. Drug abuse is well known to recruit components of the mesolimbic dopamine system, including the nucleus accumbens and ventral tegmental area. In addition, altered function of a wide variety of brain regions is tightly associated with specific manifestations of drug abuse. These regions peripheral to the mesolimbic pathway likely play a role in specific observed comorbidities and endophenotypes that can facilitate, or be caused by, substance abuse. Alterations in synaptic structure, function and connectivity, as well as epigenetic and genetic mechanisms are thought to underlie the pathologies of addiction. In preclinical models, these persistent changes are studied at the levels of molecular pharmacology and biochemistry, ex vivo and in vivo electrophysiology, radiography and behavior. Coordinating research efforts across these disciplines and examining cell type- and circuit-specific phenomena are crucial components for translating preclinical findings to viable medical interventions that effectively treat addiction and related disorders.
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影响因子：
4.8
作者：
Costa, Vincent D.;Lang, Peter J.;Sabatinelli, Dean;Versace, Francesco;Bradley, Margaret M.
通讯作者：
Bradley, Margaret M.
影响因子：
3.3
作者：
Bari, AA;Pierce, RC
通讯作者：
Pierce, RC
影响因子：
5.3
作者：
Baptista, MAS;Martin-Fardon, R;Weiss, F
通讯作者：
Weiss, F
影响因子：
3.4
作者：
Burgdorf, J;Knutson, B;Shippenberg, TS
通讯作者：
Shippenberg, TS
影响因子：
2.3
作者：
Alcantara, Adriana A.;Lim, Helen Y.;Floyd, Christopher E.;Garces, Juanita;Mendenhall, John M.;Lyons, Chelsea L.;Berlanga, Monica L.
通讯作者：
Berlanga, Monica L.