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Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters
Neuropsychopharmacology ( IF 7.6 ) Pub Date : 2023-12-07 , DOI: 10.1038/s41386-023-01773-3
Jude A. Frie , Patrick McCunn , Amr Eed , Ahmad Hassan , Karling R. Luciani , Chuyun Chen , Rachel F. Tyndale , Jibran Y. Khokhar

Though vaping likely represents a safer alternative to smoking, it is not without risks, many of which are not well understood, especially for vulnerable populations. Here we evaluate the sex- and age-dependent effects of JUUL nicotine vapour in rats. Following passive nicotine vapour exposures (from 59 mg/ml JUUL nicotine pods), rats were evaluated for reward-like behaviour, locomotion, and precipitated withdrawal. Pharmacokinetics of nicotine and its metabolites in brain and plasma and the long-term impact of nicotine vapour exposure on functional magnetic resonance imaging-based brain connectivity were assessed. Adult female rats acquired conditioned place preference (CPP) at a high dose (600 s of exposure) of nicotine vapour while female adolescents, as well as male adults and adolescents did not. Adult and adolescent male rats displayed nicotine vapour-induced precipitated withdrawal and hyperlocomotion, while both adult and adolescent female rats did not. Adult females showed higher venous and arterial plasma and brain nicotine and nicotine metabolite concentrations compared to adult males and adolescent females. Adolescent females showed higher brain nicotine concentration compared to adolescent males. Both network-based statistics and between-component group connectivity analyses uncovered reduced connectivity in nicotine-exposed rats, with a significant group by sex interaction observed in both analyses. The short- and long-term effects of nicotine vapour are affected by sex and age, with distinct behavioural, pharmacokinetic, and altered network connectivity outcomes dependent on these variables.



中文翻译:

影响JUUL电子烟尼古丁蒸气诱导大鼠奖赏、戒断、药代动力学和大脑连接的因素:性很重要

尽管电子烟可能是比吸烟更安全的替代品,但它并非没有风险,其中许多风险尚未得到充分了解,特别是对于弱势群体而言。在这里,我们评估了 JUUL 尼古丁蒸气对大鼠的性别和年龄依赖性影响。被动接触尼古丁蒸气(来自 59 mg/ml JUUL 尼古丁荚)后,对大鼠的奖励样行为、运动和突然戒断进行评估。评估了尼古丁及其代谢物在大脑和血浆中的药代动力学,以及尼古丁蒸气暴露对基于功能磁共振成像的大脑连接的长期影响。成年雌性大鼠在高剂量(暴露 600 秒)尼古丁蒸气时获得了条件性位置偏爱(CPP),而雌性青少年以及雄性成年和青少年则没有。成年和青少年雄性大鼠表现出尼古丁蒸气诱导的突然戒断和过度运动,而成年和青少年雌性大鼠则没有。与成年男性和青少年女性相比,成年女性的静脉和动脉血浆以及脑内尼古丁和尼古丁代谢物浓度较高。与青春期男性相比,青春期女性的大脑尼古丁浓度更高。基于网络的统计数据和组间连接性分析均发现尼古丁暴露大鼠的连接性降低,并且在这两项分析中观察到显着的性别相互作用。尼古丁蒸气的短期和长期影响受到性别和年龄的影响,不同的行为、药代动力学和改变的网络连接结果取决于这些变量。

更新日期:2023-12-07
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