尼古丁型乙酰胆碱受体在酒精相关行为中的作用。
The role of nicotinic acetylcholine receptors in alcohol-related behaviors.
机构信息
Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, United States.
Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, United States.
出版信息
Brain Res Bull. 2020 Oct;163:135-142. doi: 10.1016/j.brainresbull.2020.07.017. Epub 2020 Jul 22.
Abstract
Alcohol use disorder (AUD) causes an alarming economic and health burden in the United States. Unfortunately, this disease does not exist in isolation; AUD is highly comorbid with nicotine use. Results from both human and animal models demonstrate a genetic correlation between alcohol and nicotine behaviors. These data support the idea of shared genetic and neural mechanisms underlying these behaviors. Nicotine acts directly at nicotinic acetylcholine receptors (nAChR) to have its pharmacological effect. Interestingly, alcohol also acts both directly and indirectly at these receptors. Research utilizing genetically engineered rodents and pharmacological manipulations suggest a role for nAChR in several ethanol behaviors. The current manuscript collates this literature and discusses findings that implicate specific nAChR subunits in ethanol phenotypes. These data suggest future directions for targeting nAChR as novel therapeutics for AUD.
摘要
酒精使用障碍（AUD）在美国造成了惊人的经济和健康负担。不幸的是，这种疾病并不是孤立存在的；AUD 与尼古丁使用高度共病。来自人类和动物模型的结果都表明，酒精和尼古丁行为之间存在遗传相关性。这些数据支持了这些行为背后存在共同的遗传和神经机制的观点。尼古丁通过直接作用于烟碱型乙酰胆碱受体（nAChR）来发挥其药理学作用。有趣的是，酒精也直接和间接作用于这些受体。利用基因工程啮齿动物和药理学操作的研究表明，nAChR 在几种乙醇行为中起作用。本文汇集了这些文献，并讨论了表明特定 nAChR 亚基与乙醇表型相关的发现。这些数据为将 nAChR 作为 AUD 的新型治疗靶点提供了未来的方向。
相似文献
1
The role of nicotinic acetylcholine receptors in alcohol-related behaviors.尼古丁型乙酰胆碱受体在酒精相关行为中的作用。
Brain Res Bull. 2020 Oct;163:135-142. doi: 10.1016/j.brainresbull.2020.07.017. Epub 2020 Jul 22.
2
Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction.烟碱型乙酰胆碱受体与尼古丁成瘾：简介。
Neuropharmacology. 2020 Oct 15;177:108256. doi: 10.1016/j.neuropharm.2020.108256. Epub 2020 Jul 29.
3
Neuronal nicotinic receptor ligands modulate chronic nicotine-induced ethanol consumption in C57BL/6J mice.神经元烟碱型受体配体调节 C57BL/6J 小鼠慢性尼古丁诱导的乙醇消耗。
Pharmacol Biochem Behav. 2012 Jul;102(1):36-43. doi: 10.1016/j.pbb.2012.03.017. Epub 2012 Mar 27.
4
The role of nicotinic receptors in alcohol consumption.尼古丁受体在酒精消费中的作用。
Pharmacol Res. 2023 Apr;190:106705. doi: 10.1016/j.phrs.2023.106705. Epub 2023 Feb 20.
5
Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders.神经元烟碱型乙酰胆碱受体作为治疗酒精使用障碍的药物治疗靶点。
CNS Neurol Disord Drug Targets. 2010 Mar;9(1):60-76. doi: 10.2174/187152710790966597.
6
Molecular mechanisms underlying behaviors related to nicotine addiction.与尼古丁成瘾相关行为的分子机制。
Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a012112. doi: 10.1101/cshperspect.a012112.
7
Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: converging evidence from human and animal research.烟碱型乙酰胆碱受体的遗传变异性与尼古丁成瘾：来自人类和动物研究的一致证据。
Behav Brain Res. 2008 Nov 3;193(1):1-16. doi: 10.1016/j.bbr.2008.05.006. Epub 2008 May 16.
8
Chronic ethanol treatment decreases [3H]epibatidine and [3H]nicotine binding and differentially regulates mRNA levels of nicotinic acetylcholine receptor subunits expressed in M10 and SH-SY5Y neuroblastoma cells.慢性乙醇处理可降低[3H]依博加碱和[3H]尼古丁的结合，并差异调节M10和SH-SY5Y神经母细胞瘤细胞中表达的烟碱型乙酰胆碱受体亚基的mRNA水平。
J Neurochem. 1998 Mar;70(3):1134-42. doi: 10.1046/j.1471-4159.1998.70031134.x.
9
Nicotinic receptors in non-human primates: Analysis of genetic and functional conservation with humans.非人灵长类动物中的烟碱受体：与人类的遗传和功能保守性分析。
Neuropharmacology. 2015 Sep;96(Pt B):263-73. doi: 10.1016/j.neuropharm.2015.01.023. Epub 2015 Feb 7.
10
Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior.亚基选择性烟碱型乙酰胆碱受体对操作性乙醇自我给药及复发样乙醇饮用行为的影响。
Psychopharmacology (Berl). 2009 Mar;203(1):99-108. doi: 10.1007/s00213-008-1375-5. Epub 2008 Nov 6.
引用本文的文献
1
Role of glial cells in neurotoxicological effects of alcohol.神经胶质细胞在酒精神经毒理学效应中的作用。
Adv Neurotoxicol. 2025;14:41-73. doi: 10.1016/bs.ant.2025.03.001. Epub 2025 Apr 11.
2
A single-cell genomic atlas for the effects of chronic ethanol exposure in the mouse dorsal striatum.小鼠背侧纹状体慢性乙醇暴露影响的单细胞基因组图谱。
Mol Psychiatry. 2025 Apr 16. doi: 10.1038/s41380-025-03014-z.
3
Reduced brain network segregation in alcohol use disorder: Associations with neurocognition.酒精使用障碍中大脑网络分离减少：与神经认知的关联。
Addict Biol. 2024 Dec;29(12):e13446. doi: 10.1111/adb.13446.
4
Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.特定的 Chrna5 突变将酗酒与 I/II 型易感性特征和 IPN GABA 能神经元联系起来。
Transl Psychiatry. 2024 Nov 6;14(1):461. doi: 10.1038/s41398-024-03164-8.
5
Voluntary nicotine consumption and reward in a subset of diversity outbred founder strains.自愿尼古丁消费和奖励在多样性远交创始品系的一个亚群中。
J Psychopharmacol. 2024 Nov;38(11):1007-1015. doi: 10.1177/02698811241269691. Epub 2024 Aug 13.
6
Ethanol's impact on the brain: a neurobiological perspective on the mechanisms of memory impairment.乙醇对大脑的影响：记忆损伤机制的神经生物学观点。
Mol Biol Rep. 2024 Jun 25;51(1):782. doi: 10.1007/s11033-024-09748-3.
7
Adolescent intermittent alcohol exposure produces strain-specific cross-sensitization to nicotine and other behavioral adaptations in adulthood in C57BL/6J and DBA/2J mice.青少年间歇性酒精暴露会导致 C57BL/6J 和 DBA/2J 小鼠成年后对尼古丁和其他行为适应性产生菌株特异性交叉敏感。
Pharmacol Biochem Behav. 2023 Nov;232:173655. doi: 10.1016/j.pbb.2023.173655. Epub 2023 Oct 5.
8
The GlyT1-inhibitor Org 24598 facilitates the alcohol deprivation abolishing and dopamine elevating effects of bupropion + varenicline in rats.甘氨酸转运体 1 抑制剂 Org 24598 增强丁丙诺啡和伐尼克兰在大鼠体内的酒精戒断和多巴胺升高作用。
J Neural Transm (Vienna). 2024 Jan;131(1):95-106. doi: 10.1007/s00702-023-02701-x. Epub 2023 Sep 29.
9
Hippocampal place cell remapping occurs with memory storage of aversive experiences.海马位置细胞的重映射发生在对厌恶经历的记忆存储中。
Elife. 2023 Jul 19;12:e80661. doi: 10.7554/eLife.80661.
10
The role of nicotinic receptors in alcohol consumption.尼古丁受体在酒精消费中的作用。
Pharmacol Res. 2023 Apr;190:106705. doi: 10.1016/j.phrs.2023.106705. Epub 2023 Feb 20.
本文引用的文献
1
Reduced expression of ethanol sensitization by α3β4 nicotinic acetylcholine receptors in DBA/2J mice.DBA/2J小鼠中α3β4烟碱型乙酰胆碱受体对乙醇敏感性的表达降低。
Exp Clin Psychopharmacol. 2020 Jun;28(3):348-354. doi: 10.1037/pha0000324. Epub 2019 Oct 3.
2
Alpha6-containing nicotinic acetylcholine receptor is a highly sensitive target of alcohol.含阿尔法 6 的烟碱型乙酰胆碱受体是酒精的一个高度敏感的靶点。
Neuropharmacology. 2019 May 1;149:45-54. doi: 10.1016/j.neuropharm.2019.01.021. Epub 2019 Jan 30.
3
The α3β4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL/6J mice.α3β4 烟碱型乙酰胆碱受体拮抗剂 18-甲氧基高乌甲素可减少成年 C57BL/6J 小鼠的 binge 样乙醇消耗。
Alcohol. 2019 Sep;79:1-6. doi: 10.1016/j.alcohol.2018.11.006. Epub 2018 Nov 26.
4
Differential regulation of alcohol taking and seeking by antagonism at α4β2 and α3β4 nAChRs.通过拮抗 α4β2 和 α3β4 nAChR 对酒精摄入和觅药行为的差异调节。
Psychopharmacology (Berl). 2018 Jun;235(6):1745-1757. doi: 10.1007/s00213-018-4883-y. Epub 2018 Mar 23.
5
The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice without affecting concurrent nicotine consumption.烟碱型乙酰胆碱受体药物 sazetidine-A 可减少小鼠的酒精摄入量，而不影响同时摄入的尼古丁量。
Neuropharmacology. 2018 May 1;133:63-74. doi: 10.1016/j.neuropharm.2018.01.019. Epub 2018 Feb 2.
6
Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial.伐伦克林联合医学管理对合并吸烟的酒精使用障碍的疗效：一项随机临床试验。
JAMA Psychiatry. 2018 Feb 1;75(2):129-138. doi: 10.1001/jamapsychiatry.2017.3544.
7
Highly Selective and Potent α4β2 nAChR Antagonist Inhibits Nicotine Self-Administration and Reinstatement in Rats.高度选择性和强效的α4β2 nAChR 拮抗剂抑制大鼠的尼古丁自我给药和复吸。
J Med Chem. 2017 Dec 28;60(24):10092-10104. doi: 10.1021/acs.jmedchem.7b01250. Epub 2017 Dec 13.
8
The Effects of Long-Term Varenicline Administration on Ethanol and Sucrose Seeking and Self-Administration in Male P Rats.长期给予伐伦克林对雄性 P 大鼠乙醇和蔗糖觅药和自身给药的影响。
Alcohol Clin Exp Res. 2018 Feb;42(2):453-460. doi: 10.1111/acer.13562. Epub 2017 Dec 23.
9
α6 subunit-containing nicotinic receptors mediate low-dose ethanol effects on ventral tegmental area neurons and ethanol reward.含α6 亚基的烟碱型乙酰胆碱受体介导低剂量乙醇对腹侧被盖区神经元和乙醇奖赏的影响。
Addict Biol. 2018 Sep;23(5):1079-1093. doi: 10.1111/adb.12559. Epub 2017 Sep 13.
10
The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation.内侧缰核与脚间核神经回路在成瘾、焦虑和情绪调节中起关键作用。
J Neurochem. 2017 Aug;142 Suppl 2(Suppl 2):130-143. doi: 10.1111/jnc.14008.
Zotero 插件