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早期青少年尼古丁暴露会影响雄性小鼠晚年海马体 μ-阿片受体活性和吗啡奖赏,但不会影响身体依赖。

Early adolescent nicotine exposure affects later-life hippocampal mu-opioid receptors activity and morphine reward but not physical dependence in male mice.

机构信息

Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23219, USA.

Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23219, USA.

出版信息

Pharmacol Biochem Behav. 2018 Oct;173:58-64. doi: 10.1016/j.pbb.2018.08.006. Epub 2018 Aug 17.

DOI:10.1016/j.pbb.2018.08.006
PMID:30125591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6160313/
Abstract

RATIONALE

There is extensive literature regarding nicotine-opioid functional interactions. The possibility that use of nicotine products during adolescence might increase the risk of substance abuse such as morphine later in adulthood is particularly relevant to the current opioid crisis.

OBJECTIVES

To investigate the effects of nicotine exposure for seven days during adolescence in mice on morphine reward as well as morphine physical dependence later in adulthood.

METHODS

Mice were exposed to nicotine in either early or late adolescence then evaluated for morphine reward and withdrawal symptoms in adulthood. A separate group of mice was exposed to nicotine during adolescent and tissue was evaluated for changes in MOR-mediated G-protein activity using [S]GTPγS binding assays.

RESULTS

We report that a 7-day exposure to a low dose of nicotine during early adolescence significantly enhanced morphine preference in the CPP test in adult mice. In contrast, the same treatment with nicotine had no effect on expression of somatic withdrawal signs in morphine-dependent adult mice. MOR-mediated G-protein activity in hippocampus, but not thalamus and striatum of adult mice, was significantly altered by adolescent nicotine treatment.

CONCLUSIONS

Adolescence is a unique developmental stage during which nicotine has long-term effects on future drug-taking behavior. Further studies are needed to identify the neurotransmitters and mechanisms involved in increased vulnerability to drug abuse.

摘要

背景

有大量关于尼古丁-阿片类药物功能相互作用的文献。青少年时期使用尼古丁产品可能会增加成年后滥用药物(如吗啡)的风险,这一点尤其与当前的阿片类药物危机有关。

目的

研究在青春期的 7 天内暴露于尼古丁对成年后吗啡奖赏以及吗啡躯体依赖的影响。

方法

将小鼠暴露于早期或晚期青春期的尼古丁中,然后在成年期评估其对吗啡奖赏和戒断症状的反应。另一组小鼠在青春期期间暴露于尼古丁中,并使用[S]GTPγS 结合测定法评估 MOR 介导的 G 蛋白活性的变化。

结果

我们报告称,在青春期早期暴露于低剂量尼古丁 7 天显著增强了成年小鼠在 CPP 测试中的吗啡偏好。相比之下,同样的尼古丁处理对成年吗啡依赖小鼠的躯体戒断症状的表达没有影响。成年小鼠海马体中 MOR 介导的 G 蛋白活性,但丘脑和纹状体中没有,被青春期尼古丁处理显著改变。

结论

青春期是一个独特的发育阶段,在此期间,尼古丁对未来的药物使用行为有长期影响。需要进一步研究以确定涉及药物滥用易感性增加的神经递质和机制。

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本文引用的文献

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Opioid Abuse in Chronic Pain--Misconceptions and Mitigation Strategies.慢性疼痛中的阿片类药物滥用——误解与缓解策略
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Neuropharmacology. 2016 Jun;105:308-317. doi: 10.1016/j.neuropharm.2016.01.032. Epub 2016 Jan 22.
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Adolescent nicotine exposure fails to impact cocaine reward, aversion and self-administration in adult male rats.青春期尼古丁暴露对成年雄性大鼠的可卡因奖赏、厌恶反应及自我给药行为没有影响。
Pharmacol Biochem Behav. 2015 Oct;137:30-7. doi: 10.1016/j.pbb.2015.08.004. Epub 2015 Aug 6.
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Adolescent nicotine induces persisting changes in development of neural connectivity.青少年尼古丁会导致神经连接发育的持续变化。
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The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies.α3β4*烟碱型乙酰胆碱受体亚型介导对吗啡的身体依赖性:小鼠和人体研究。
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Juvenile ethanol exposure increases rewarding properties of cocaine and morphine in adult DBA/2J mice.幼年乙醇暴露增加成年 DBA/2J 小鼠中海洛因和吗啡的奖赏效应。
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