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雄性大鼠青春期接触吗啡会改变雄性子代蓝斑神经元的电生理特性。

Adolescent Morphine Exposure in Male Rats Alters the Electrophysiological Properties of Locus Coeruleus Neurons of the Male Offspring.

机构信息

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Neuroscience. 2019 Jul 1;410:108-117. doi: 10.1016/j.neuroscience.2019.05.009. Epub 2019 May 12.

Abstract

Opioid prescription and illegal use have been soaring, and it has become a global concern. Adolescence, as a critical developmental period, is radically influenced by drug exposure. In the recent decade, transgenerational effects of paternal environmental exposure have been given greater consideration. There is compelling evidence for the effect of paternal drug abuse such as alcohol, cocaine, and nicotine on the offspring; however, a limited number of studies have focused on the paternal effect of opioids during adolescence on progeny. Locus coeruleus (LC) is a noradrenergic nucleus involved in different brain functions and cognitive processes. The present study aimed to investigate the transgenerational effect of adolescent morphine exposure on electrophysiological properties of LC neurons of the offspring. For this purpose, adolescent male rats received morphine or saline for 10 days between postnatal days 31 and 40, and then after 20 days of washout period, they were mated with naïve female rats. Whole cell patch clamp recordings were performed in current clamp configuration from LC neurons of 14-21-day-old male offspring. The results demonstrated that the decay slope of the action potentials and the amplitude of afterhyperpolarization potential increased in morphine sired animals. Moreover, the duration of action potentials decreased in morphine sired animals. Besides, the coefficient of variation of interspike intervals increased in morphine sired animals compared to the saline sired ones. Overall, the altered electrophysiological properties observed in this study may suggest a functional enhancement of Ca activated K channels in LC neurons of morphine sired animals.

摘要

阿片类药物处方和非法使用呈飙升趋势,已成为全球关注的焦点。青春期是一个关键的发育时期,会受到药物暴露的极大影响。在最近十年中,人们越来越关注父代环境暴露的跨代效应。有确凿的证据表明,父代滥用酒精、可卡因和尼古丁等药物会对后代产生影响;然而,很少有研究关注父代在青春期滥用阿片类药物对后代的影响。蓝斑(LC)是一个涉及不同大脑功能和认知过程的去甲肾上腺素核。本研究旨在探讨青春期吗啡暴露对后代 LC 神经元电生理特性的跨代效应。为此,雄性幼鼠在出生后第 31 天至第 40 天期间接受吗啡或生理盐水治疗 10 天,然后在洗脱期 20 天后与未接受处理的雌性大鼠交配。在电流钳模式下对 14-21 日龄雄性幼鼠的 LC 神经元进行全细胞膜片钳记录。结果表明,吗啡亲代动物的动作电位衰减斜率和后超极化电位幅度增加,动作电位持续时间缩短。此外,与生理盐水亲代动物相比,吗啡亲代动物的峰间间隔变异系数增加。总的来说,与生理盐水亲代动物相比,吗啡亲代动物 LC 神经元观察到的电生理特性改变可能提示 Ca 激活的 K 通道功能增强。

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