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青少年接触尼古丁会影响小鼠成年后的尼古丁奖赏和戒断反应。

Adolescent nicotine exposure affects later-life nicotine reward and withdrawal in mice.

作者信息

Buzzi Belle, Buttar Burhan, Groener Yasmine, Damaj M Imad

机构信息

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States of America.

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States of America.

出版信息

Pharmacol Biochem Behav. 2025 Oct;255:174061. doi: 10.1016/j.pbb.2025.174061. Epub 2025 Jul 10.

DOI:10.1016/j.pbb.2025.174061
PMID:40651536
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12381863/
Abstract

Commencement of smoking at an early age increases the number of cigarettes smoked per day and decreases the likelihood of successful cessation later in life. To date, little is known about the effects that adolescent nicotine exposure has on aspects of nicotine dependence in adulthood. In this study, we examined the effects of adolescent nicotine exposure on nicotine reward and withdrawal in adulthood. Adolescent mice [postnatal day (PND) 28-34] were exposed to nicotine short-term (0.5 mg/kg, subcutaneous (s.c.) twice a day for one day) or repeatedly (0.1 and 0.5 mg/kg, s.c. twice daily for seven days). In adulthood (PND 70) these mice were implanted with osmotic nicotine minipumps for 14 days and 24 h later spontaneous nicotine withdrawal affective (anxiety-like behavior and hyperalgesia) and physical (somatic signs) signs were assessed. Short-term pre-exposure to nicotine during adolescence did not produce alterations in affective or physical nicotine withdrawal signs in adulthood. However, repeated nicotine exposure during adolescence partially reduced nicotine withdrawal signs in adulthood but increases nicotine reward in the conditioned place preference (CPP) test. Interestingly, adult mice exposed to chronic nicotine (0.5 mg/kg,s.c. twice daily for seven days) did not affect nicotine withdrawal signs and reward later in adulthood. This mouse study highlights nicotine exposure during the unique period of adolescence as an important factor for nicotine dependence later in life.

摘要

早年开始吸烟会增加每日吸烟量,并降低日后成功戒烟的可能性。迄今为止,对于青少年接触尼古丁对成年期尼古丁依赖各方面的影响知之甚少。在本研究中,我们检测了青少年接触尼古丁对成年期尼古丁奖赏和戒断的影响。将青春期小鼠[出生后第(PND)28 - 34天]短期(0.5毫克/千克,皮下注射(s.c.),每天两次,共一天)或反复(0.1和0.5毫克/千克,皮下注射,每天两次,共七天)暴露于尼古丁。成年期(PND 70)时,给这些小鼠植入渗透式尼古丁微型泵14天,24小时后评估自发尼古丁戒断的情感(类似焦虑行为和痛觉过敏)和身体(躯体症状)症状。青春期短期预先接触尼古丁并未导致成年期情感或身体尼古丁戒断症状出现改变。然而,青春期反复接触尼古丁可部分减轻成年期尼古丁戒断症状,但在条件性位置偏爱(CPP)试验中增加尼古丁奖赏。有趣的是,成年小鼠长期接触尼古丁(0.5毫克/千克,皮下注射,每天两次,共七天)对成年后期的尼古丁戒断症状和奖赏没有影响。这项小鼠研究强调了青春期这一独特时期接触尼古丁是成年后期尼古丁依赖的一个重要因素。

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本文引用的文献

1
Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice.小鼠新型口鼻受限尼古丁雾化自我给药模型的表征
Neuropharmacology. 2025 May 1;268:110315. doi: 10.1016/j.neuropharm.2025.110315. Epub 2025 Jan 18.
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Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state.早期青春期雄性小鼠短暂的尼古丁暴露会使他们的多巴胺回路处于不成熟状态。
Nat Commun. 2024 Oct 18;15(1):9017. doi: 10.1038/s41467-024-53327-w.
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Nicotine and fluoxetine alter adolescent dopamine-mediated behaviors via 5-HT receptor activation.尼古丁和氟西汀通过5-羟色胺受体激活改变青少年多巴胺介导的行为。
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Post-weaning social isolation increases the incentive value of nicotine-related contexts and decreases the accumulation of ΔFosB in nucleus accumbens in adolescent rats.断乳后社交隔离增加了与尼古丁相关的环境的激励价值,并减少了青春期大鼠伏隔核中 ΔFosB 的积累。
Pharmacol Biochem Behav. 2023 Feb;223:173529. doi: 10.1016/j.pbb.2023.173529. Epub 2023 Feb 17.
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Age-dependent effects of tobacco smoke and nicotine on cognition and the brain: A systematic review of the human and animal literature comparing adolescents and adults.烟草烟雾和尼古丁对认知及大脑的年龄依赖性影响:对比较青少年和成年人的人类及动物文献的系统综述
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Adolescent nicotine administration increases nicotinic acetylcholine receptor binding and functional connectivity in specific cortico-striatal-thalamic circuits.青少年尼古丁给药增加了特定皮质-纹状体-丘脑回路中的烟碱型乙酰胆碱受体结合及功能连接性。
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Smoking and E-Cigarette Use Among U.S. Adults During the COVID-19 Pandemic.美国成年人在 COVID-19 大流行期间的吸烟和电子烟使用情况。
Am J Prev Med. 2022 Mar;62(3):341-349. doi: 10.1016/j.amepre.2021.08.018. Epub 2021 Oct 6.
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Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence.神经回路和烟碱型乙酰胆碱受体介导中脑多巴胺神经元的胆碱能调节和尼古丁依赖。
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