Masrouri Hossein, Azadi Maryam, Semnanian Saeed, Azizi Hossein
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Brain Res Bull. 2021 Apr;169:128-135. doi: 10.1016/j.brainresbull.2021.01.011. Epub 2021 Jan 19.
Early life stress can serve as one of the principle sources leading to individual differences in confronting challenges throughout the lifetime. Maternal deprivation (MD), a model of early life stress, can cause persistent alterations in brain function, and it may constitute a risk factor for later incidence of drug addiction. It is becoming more apparent that early life MD predisposes opiate abuse in adulthood. Although several behavioral and molecular studies have addressed this issue, changes in electrophysiological features of the neurons are yet to be understood. The lateral paragigantocellularis (LPGi) nucleus, which participates in the mediation of opiate dependence and withdrawal, may be susceptible to modifications following MD. This study sought to find whether early life MD can alter the discharge activity of LPGi neurons and their response to acute morphine administration in adult rats. Male Wistar rats experienced MD on postnatal days (PNDs) 1-14 for three h per day. Afterward, they were left undisturbed until PND 70, during which the extracellular activities of LPGi neurons were recorded in anesthetized animals at baseline and in response to acute morphine. In both MD and control groups, acute morphine administration induced heterogeneous (excitatory, inhibitory, and no effect) responses in LPGi neurons. At baseline recording, the interspike interval variability of the LPGi neurons was attenuated in both inhibitory and excitatory responses in animals with the history of MD. The extent of morphine-induced discharge inhibition was also lower in deprived animals compared to the control group. These findings suggest that early life MD induces long-term alterations in LPGi neuronal activity in response to acute administration of morphine. Therefore, the MD may alter the vulnerability to develop opiate abuse in adulthood.
早期生活应激可能是导致个体在应对一生挑战时出现差异的主要根源之一。母婴分离（MD）作为一种早期生活应激模型，可导致大脑功能的持续改变，并且可能构成后期药物成瘾的一个风险因素。越来越明显的是，早期生活母婴分离会使成年后更容易出现阿片类药物滥用。尽管多项行为学和分子学研究已探讨了这一问题，但神经元电生理特征的变化仍有待了解。参与介导阿片类药物依赖和戒断的外侧巨细胞旁核（LPGi）可能在母婴分离后易发生改变。本研究旨在探究早期生活母婴分离是否会改变成年大鼠LPGi神经元的放电活动及其对急性给予吗啡的反应。雄性Wistar大鼠在出生后第1 - 14天每天经历3小时的母婴分离。之后，让它们不受干扰直至出生后第70天，在此期间，在麻醉动物的基线状态下以及对急性吗啡的反应中记录LPGi神经元的细胞外活动。在母婴分离组和对照组中，急性给予吗啡均在LPGi神经元中诱导出异质性（兴奋性、抑制性和无效应）反应。在基线记录时，有母婴分离史的动物中，LPGi神经元在抑制性和兴奋性反应中的峰间间期变异性均减弱。与对照组相比，剥夺组动物中吗啡诱导的放电抑制程度也较低。这些发现表明，早期生活母婴分离会在急性给予吗啡时诱导LPGi神经元活动发生长期改变。因此，母婴分离可能会改变成年后发生阿片类药物滥用的易感性。
