Divisions of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA; Departments of Physiology, Shantou University Medical College, Shantou, Guangdong, China.
Biochem Pharmacol. 2013 Oct 15;86(8):1173-80. doi: 10.1016/j.bcp.2013.07.013. Epub 2013 Aug 7.
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 from in vitro studies, 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 under in vivo conditions have received only limited attention. Building upon the existing knowledge acquired in 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.
吸烟是一个主要的公共卫生问题。尼古丁作用于大脑中广泛分布的烟碱型乙酰胆碱受体（nAChRs），并兴奋腹侧被盖区（VTA）中的多巴胺（DA）神经元。所引起的 DA 神经元活动增加被认为是尼古丁奖赏的重要机制，随后是成瘾的转变。然而，目前对尼古丁奖赏的理解主要基于从体外研究中积累的数据，通常来自 VTA 切片。分离的 VTA 切片人为地终止了 VTA 中和其他大脑区域之间的神经元通讯，这可能会显著改变烟碱的作用。因此，在体内条件下 VTA DA 神经元烟碱兴奋的机制仅受到了有限的关注。在体外获得的现有知识的基础上，现在是时候阐明在更能理解尼古丁或其他成瘾性药物作用的完整系统中烟碱奖赏的整合机制了。在这篇综述中，我们总结了最近的研究，这些研究表明前额叶皮层（PFC）对 VTA DA 神经元功能和尼古丁奖赏的调节作用。基于现有证据，我们提出了一个新的假设，即 PFC-VTA 功能耦合作为尼古丁奖赏的整合机制。此外，成瘾可能是由于尼古丁扰乱了 PFC-VTA 偶联，从而消除了 PFC 对行为的认知控制。
