Cortical control of VTA function and influence on nicotine reward.
Cortical control of VTA function and influence on nicotine reward.
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DOI：
10.1016/j.bcp.2013.07.013
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发表时间：
2013-10
影响因子：
5.8
通讯作者：
Jie Wu;M. Gao;Jian‐xin Shen;W. Shi;A. Oster;B. Gutkin
中科院分区：
文献类型：
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作者：
Jie Wu;M. Gao;Jian‐xin Shen;W. Shi;A. Oster;B. Gutkin
烟草使用是一个重大的公共卫生问题。尼古丁作用于大脑中广泛分布的尼古丁乙酰胆碱受体（nAChRs），刺激腹侧被盖区（VTA）的多巴胺（DA）神经元。DA神经元活动的增加被认为是尼古丁奖励和随后过渡到成瘾的重要机制。然而，目前对尼古丁奖励的理解主要是基于体外研究积累的数据，通常来自VTA切片。孤立的VTA切片人为地终止了VTA和其他大脑区域神经元之间的通信，这些通信可能会显著改变尼古丁的影响。因此，在活体条件下，VTA - DA神经元的尼古丁兴奋机制只受到有限的关注。基于在体外获得的现有知识，现在是时候阐明尼古丁奖励对完整系统的综合机制，这与理解尼古丁或其他成瘾药物的作用更相关。本文综述了近年来有关前额叶皮层（PFC）对VTA - DA神经元功能和尼古丁奖励调节的影响。基于现有证据，我们提出PFC-VTA功能耦合是尼古丁奖励的整合机制的新假设。此外，由于尼古丁干扰PFC-VTA偶联，从而消除了pfc依赖性对行为的认知控制，成瘾可能会发生。
Tobacco use is a major public health problem. Nicotine acts on widely distributed nicotinic acetylcholine receptors (nAChRs) in the brain and excites dopamine (DA) neurons in the ventral tegmental area (VTA). The elicited increase of DA neuronal activity is thought to be an important mechanism for nicotine reward and subsequently the transition to addiction. However, the current understanding of nicotine reward is based predominantly on the data accumulated fromin vitrostudies, often from VTA slices. Isolated VTA slices artificially terminate communications between neurons in the VTA and other brain regions that may significantly alter nicotinic effects. Consequently, the mechanisms of nicotinic excitation of VTA DA neurons underin vivoconditions have received only limited attention. Building upon the existing knowledge acquiredin vitro, it is now time to elucidate the integrated mechanisms of nicotinic reward on intact systems that are more relevant to understanding the action of nicotine or other addictive drugs. In this review, we summarize recent studies that demonstrate the impact of prefrontal cortex (PFC) on the modulation of VTA DA neuronal function and nicotine reward. Based on existing evidence, we propose a new hypothesis that PFC–VTA functional coupling serves as an integration mechanism for nicotine reward. Moreover, addiction may develop due to nicotine perturbing the PFC–VTA coupling and thereby eliminating the PFC-dependent cognitive control over behavior.