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产前暴露于吗啡可增强蓝斑核神经元的兴奋性。

Prenatal exposure to morphine enhances excitability in locus coeruleus neurons.

机构信息

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

出版信息

J Neural Transm (Vienna). 2022 Aug;129(8):1049-1060. doi: 10.1007/s00702-022-02515-3. Epub 2022 Jun 8.

Abstract

Opioid abuse during pregnancy may have noteworthy effects on the child's behavioral, emotional and cognitive progression. In this study, we assessed the effect of prenatal exposure to morphine on electrophysiological features of locus coeruleus (LC) noradrenergic neurons which is involved in modulating cognitive performance. Pregnant dams were randomly divided into two groups, that is a prenatal saline treated and prenatal morphine-treated group. To this end, on gestational days 11-18, either morphine or saline (twice daily, s.c.) was administered to pregnant dams. Whole-cell patch-clamp recordings were conducted on LC neurons of male offspring. The evoked firing rate, instantaneous frequency and action potentials half-width, and also input resistance of LC neurons significantly increased in the prenatal morphine group compared to the saline group. Moreover, action potentials decay slope, after hyperpolarization amplitude, rheobase current, and first spike latency were diminished in LC neurons following prenatal exposure to morphine. In addition, resting membrane potential, rise slope, and amplitude of action potentials were not changed by prenatal morphine exposure. Together, the current findings show a significant enhancement in excitability of the LC neurons following prenatal morphine exposure, which may affect the release of norepinephrine to other brain regions and/or cognitive performances of the offspring.

摘要

孕期阿片类药物滥用可能对儿童的行为、情绪和认知发展产生显著影响。在这项研究中,我们评估了产前暴露于吗啡对蓝斑(LC)去甲肾上腺素能神经元电生理特征的影响,蓝斑去甲肾上腺素能神经元参与调节认知表现。怀孕的母鼠被随机分为两组,即产前生理盐水处理组和产前吗啡处理组。为此,在妊娠第 11-18 天,给母鼠每日两次皮下注射吗啡或生理盐水。对雄性后代的 LC 神经元进行全细胞膜片钳记录。与生理盐水组相比,产前吗啡组 LC 神经元的诱发放电频率、瞬时频率和动作电位半宽度以及输入电阻显著增加。此外,LC 神经元在产前暴露于吗啡后,动作电位衰减斜率、超极化后幅度、阈电流和第一峰潜伏期降低。此外,静息膜电位、动作电位上升斜率和幅度不受产前吗啡暴露的影响。总之,目前的研究结果表明,产前吗啡暴露后 LC 神经元的兴奋性显著增强,这可能影响去甲肾上腺素向其他脑区的释放和/或后代的认知表现。

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