Subtypes of nicotinic acetylcholine receptors in nicotine reward, dependence, and withdrawal: evidence from genetically modified mice.
Subtypes of nicotinic acetylcholine receptors in nicotine reward, dependence, and withdrawal: evidence from genetically modified mice.
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DOI：
10.1097/fbp.0b013e32830c360e
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发表时间：
2008-09
影响因子：
1.6
通讯作者：
Kenny PJ
中科院分区：
文献类型：
--
作者：
Fowler CD;Arends MA;Kenny PJ
神经元烟碱乙酰胆碱受体（nAChR）可以调节整个中枢神经系统中许多神经递质通路的活性，并且被认为是认知和情感的重要调节剂。nAChR也是尼古丁在大脑中的主要作用部位，尼古丁是烟草烟雾的主要成瘾成分。nAChR由五个跨膜亚基（α和β同种型）组成，它们可以以各种组合结合形成功能性nAChR离子通道。由于缺乏nAChR亚型选择性配体，调节尼古丁奖赏效应和尼古丁依赖性发展的nAChR的精确亚基组成尚不清楚。然而，与遗传nAChR亚基修饰的小鼠的出现提供了一个有用的实验方法来评估个体亚基在体内的贡献。在这里，我们回顾nAChR亚基敲除和转基因小鼠产生的数据支持离散nAChR亚基在尼古丁强化和依赖过程中的作用。重要的是，与普通人群相比，患有共病精神疾病的患者的烟草依赖率要高得多，这可能至少部分反映了nAChR信号的疾病相关改变。因此，了解nAChRs在与高烟草成瘾率相关的精神疾病中的作用，可能会揭示尼古丁依赖机制的新见解。因此，我们还简要回顾了转基因小鼠产生的数据，以支持离散的nAChR亚基在焦虑症，抑郁症和精神分裂症中的作用。
Neuronal nicotinic acetylcholine receptors (nAChRs) can regulate the activity of many neurotransmitter pathways throughout the central nervous system and are considered important modulators of cognition and emotion. nAChRs also are the primary site of action in the brain for nicotine, the major addictive component of tobacco smoke. nAChRs consist of five membrane-spanning subunits (α and β isoforms) that can associate in various combinations to form functional nAChR ion channels. Because of a dearth of nAChR subtype-selective ligands, the precise subunit composition of the nAChRs that regulate the rewarding effects of nicotine and the development of nicotine dependence are unknown. However, the advent of mice with genetic nAChR subunit modifications has provided a useful experimental approach to assess the contribution of individual subunits in vivo. Here we review data generated from nAChR subunit knockout and genetically modified mice supporting a role for discrete nAChR subunits in nicotine reinforcement and dependence processes. Importantly, the rates of tobacco dependence are far higher in patients suffering from comorbid psychiatric illnesses compared with the general population, which may at least partly reflect disease-associated alterations in nAChR signaling. An understanding of the role of nAChRs in psychiatric disorders associated with high rates of tobacco addiction, therefore, may reveal novel insights into mechanisms of nicotine dependence. Thus, we also briefly review data generated from genetically modified mice to support a role for discrete nAChR subunits in anxiety disorders, depression, and schizophrenia.