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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The beta 3 subunit of the nicotinic acetylcholine receptor is required for nicotine withdrawal-induced affective but not physical signs or nicotine reward in mice
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The beta 3 subunit of the nicotinic acetylcholine receptor is required for nicotine withdrawal-induced affective but not physical signs or nicotine reward in mice

机译：烟碱乙酰胆碱受体的β3亚基是尼古丁戒断诱导的情感而不是小鼠的物理征兆或尼古丁奖励

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Nicotinic acetylcholine receptors (nAChRs) are the primary target for nicotine, the addictive component in tobacco products. These pentameric receptors are made up of various subunits which contribute to the diverse functions of nAChR subtypes. The beta 3 subunit of the nAChR has been understudied in nicotine dependence, even though it is expressed in brain regions important for drug reward. Therefore, we assessed nicotine dependence behaviors in beta 3 wildtype (WT) and knockout (KO) male and female mice. We evaluated nicotine reward in the conditioned place preference (CPP) test and then measured nicotine withdrawal signs after chronic exposure to the drug. For the withdrawal studies, mice were continuously infused with 24 mg/kg/day of nicotine using surgically implanted osmotic mini pumps for 14 days. Mini-pumps were removed at day 15, and withdrawal signs (somatic signs, hyperalgesia, anhedonia-like measure using the sucrose preference test and anxiety-like behaviors using the light dark boxes) were collected at 24 h intervals for three days following spontaneous withdrawal of nicotine. Nicotine-induced CPP did not differ between beta 3 KO and WT mice. beta 3 KO mice displayed similar somatic symptoms and hyperalgesia compared to WT mice but showed significant absence in affective (anhedonia and anxiety-like behaviors) withdrawal signs in nicotine-dependent mice. These observations suggest that the beta 3 nicotinic subunits do not seem to influence nicotine reward but plays an important role in affective nicotine withdrawal signs. Given the health burden of tobacco use disorder and the modest effect of smoking cessation aids, it is important to understand underlying factor contributing to nicotine dependence. The results of this study will further our knowledge of the role of the beta 3 nAChR subunit in nicotine reward and withdrawal behaviors in hopes of finding new molecular targets for smoking cessation aids.
机译：烟碱乙酰胆碱受体（NACHRS）是尼古丁的主要靶标，烟草制品中的上瘾组分。这些五聚体受体由各种亚基组成，这些亚基有助于NACHR亚型的不同功能。在尼古丁的依赖中，NACHR的β3亚基已经被纳米尼依赖，即使它在脑区表达了对药物奖励的重要性。因此，我们评估了β3野生型（WT）和敲除（KO）雄性和雌性小鼠的尼古丁依赖行为。在条件的地方偏好（CPP）测试中，我们评估了尼古丁奖励，然后测量了慢性暴露于药物后的尼古丁戒断标志。对于戒断研究，使用手术植入的渗透迷你泵将小鼠连续注入24mg / kg /天尼古丁14天。在第15天拆除迷你泵，并在自发撤离后24小时收集戒断症状（使用蔗糖偏好测试和使用光暗箱的焦虑样行为和焦虑的行为的胃疗法偏好试验和焦虑的行为）。尼古丁。尼古丁诱导的CPP在β3kO和WT小鼠之间没有区别。与WT小鼠相比，β3KO小鼠展示了类似的体细胞症状和痛觉过敏，但表现出尼古丁依赖性小鼠中的情感（厌氧和焦虑的行为）戒断症状。这些观察结果表明，β3烟碱亚基似乎并不影响尼古丁奖励，但在情感尼古丁戒断症状中起着重要作用。鉴于烟草使用障碍的健康负担以及吸烟戒烟艾滋病的适度效果，了解有助于尼古丁依赖的潜在因素是很重要的。本研究的结果将进一步了解β3NACHR亚基在尼古丁奖励和戒断行为中的作用的了解，希望找到用于吸烟助剂的新分子靶标。

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    Jackson Asti B.; Toma Wisam; Contreras Katherine M.; Alkhlaif Yasmin; Damaj M. Imad;

  • 作者单位

    Virginia Commonwealth Univ Dept Pharmacol &

    Toxicol Bpx 980613 Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Pharmacol &

    Toxicol Bpx 980613 Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Pharmacol &

    Toxicol Bpx 980613 Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Pharmacol &

    Toxicol Bpx 980613 Richmond VA 23298 USA;

    Virginia Commonwealth Univ Dept Pharmacol &

    Toxicol Bpx 980613 Richmond VA 23298 USA;

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  • 正文语种 eng
  • 中图分类 药理学;
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