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哺乳期通过强制灌胃暴露于尼古丁的母鼠会导致其后代青春期风险评估降低和烟碱型乙酰胆碱受体β2 表达降低。

Reduced adolescent risk-assessment and lower nicotinic beta-2 expression in rats exposed to nicotine through lactation by forcedly drinking dams.

机构信息

Department of Cognition and Behaviour, Paris-Saclay Institute of Neuroscience, UMR 9197, CNRS and Paris-Sud University, Orsay, France.

Reference Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Neuroscience. 2019 Aug 10;413:64-76. doi: 10.1016/j.neuroscience.2019.06.014. Epub 2019 Jun 19.

DOI:10.1016/j.neuroscience.2019.06.014
PMID:31228592
Abstract

Few animal studies focus on consequences of nicotine postnatal exposure, particularly through lactation. We have recently shown that forced nicotine drinking elevates maternal care, paradoxically provoking arousal and stress in pups. Present work aimed to evaluate the specific contribution of altered maternal cares, compared to the sequelae merely due to nicotine effects. Two groups were compared to water-drinking control dams: (i) free-choice dams (H2O+NIC group) drinking from two bottles, containing either nicotine or water; (ii) forced dams (NIC+NIC group) drinking from two bottles, both containing nicotine. We previously demonstrated that nicotine was indeed transferred to the lactating offspring. Regarding behavioural consequences at adolescence, both H2O+NIC and NIC+NIC rats were slower than controls in discovering a novel over a familiar compartment, whilst only NIC+NIC rats exhibited reduced risk-related avoidance and assessment behaviour. Brain analyses at adulthood suggest that, in prefrontal cortex, nicotine per se reduced serotonin, while the maternal overcare reduced CHRN-B2 gene-expression. As a whole, unescapable nicotine-enhanced maternal care could have an impact on the offspring arousal by acting on prefrontal CHRN-B2 gene-expression. When present results are translated to consequences of non-voluntary exposure in humans, we propose that children receiving altered attentions by a smoking caregiver might undergo a neuro-behavioural development biased towards emotional shyness.

摘要

很少有动物研究关注尼古丁产后暴露的后果,特别是通过哺乳。我们最近表明,强制尼古丁摄入会增加母性行为,但这会反常地引起幼崽的觉醒和应激。目前的工作旨在评估与仅仅由于尼古丁作用而引起的后果相比,改变的母性行为的具体贡献。与饮水控制组母鼠相比,有两组接受了比较:(i)自由选择组(H2O+NIC 组)从两个瓶子中饮水,一个瓶子中含有尼古丁,另一个瓶子中含有水;(ii)强制组(NIC+NIC 组)从两个瓶子中饮水,两个瓶子中都含有尼古丁。我们之前已经证明,尼古丁确实可以转移到哺乳期的后代身上。关于青春期的行为后果,H2O+NIC 和 NIC+NIC 组的大鼠比对照组在发现新的和熟悉的隔间时都要慢,而只有 NIC+NIC 组的大鼠表现出减少的风险相关回避和评估行为。成年期的大脑分析表明,在额皮质中,尼古丁本身会降低 5-羟色胺,而过度的母性行为会降低 CHRN-B2 基因表达。总的来说,无法逃避的增强的尼古丁母性行为可能通过作用于前额叶 CHRN-B2 基因表达来影响后代的觉醒。当将这些结果转化为人类非自愿暴露的后果时,我们提出,接受吸烟照顾者改变注意力的儿童可能会经历偏向于情感害羞的神经行为发育。

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