Rahman Shafiqur, López-Hernández Gretchen Y, Corrigall William A, Papke Roger L
Department of Pharmaceutical Sciences, South Dakota State University, College of Pharmacy, Brookings, SD 57007, USA.
CNS Neurol Disord Drug Targets. 2008 Nov;7(5):422-41. doi: 10.2174/187152708786927831.
Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the United States and the rest of the world. Accumulated evidence indicates that brain nicotinic acetylcholine receptors (nAChRs) are a heterogenous family of ion channels expressed in the various parts of the brain. A growing body of preclinical studies suggests that brain nAChRs are critical targets for the development of pharmacotherapies for nicotine and other drug addictions. In this review, we will discuss the nAChR subtypes, their function in response to endogenous brain transmitters, and how their functions are regulated in the presence of nicotine. Furthermore, we will discuss the role of nAChRs in mediating nicotine-induced addictive behavior in animal models. Additionally, we will provide an overview of the effects of nicotine and nicotinic compounds on the mesolimbic dopamine system, part of the reinforcement/reward circuitry of the brain, as an example of the neurochemical basis of nicotine addiction and other drug addictions. An appreciation of the complexity of nicotinic receptors and their regulation will be necessary for the development of nicotinic receptor modulators as potential pharmacotherapy for drug addiction.
在美国及世界其他地区，尼古丁成瘾和其他形式的药物成瘾仍然是重大的公共卫生问题。越来越多的证据表明，脑烟碱型乙酰胆碱受体（nAChRs）是一类在大脑各个部位表达的异质性离子通道家族。越来越多的临床前研究表明，脑nAChRs是开发尼古丁及其他药物成瘾药物疗法的关键靶点。在这篇综述中，我们将讨论nAChR亚型、它们对内源性脑递质的反应功能，以及在存在尼古丁的情况下其功能是如何被调节的。此外，我们将讨论nAChRs在介导动物模型中尼古丁诱导的成瘾行为中的作用。此外，我们将概述尼古丁和烟碱类化合物对中脑边缘多巴胺系统的影响，中脑边缘多巴胺系统是大脑强化/奖赏回路的一部分，以此作为尼古丁成瘾和其他药物成瘾神经化学基础的一个例子。认识到烟碱受体的复杂性及其调节对于开发作为药物成瘾潜在药物疗法的烟碱受体调节剂是必要的。
