Paternal exposure to morphine during adolescence potentiates morphine withdrawal in male offspring: Involvement of the lateral paragigantocellularis nucleus
Paternal exposure to morphine during adolescence potentiates morphine withdrawal in male offspring: Involvement of the lateral paragigantocellularis nucleus
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DOI：
10.1177/0269881120953993
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发表时间：
2020-10-08
影响因子：
4.1
通讯作者：
Azizi, Hossein
中科院分区：
文献类型：
--
作者：
Azadi, Maryam;Gompf, Heinrich S.;Azizi, Hossein
背景：青春期阿片类药物暴露会扰乱大脑的成熟过程，不仅对暴露的个体，而且对他们的后代都可能产生长期的不良后果。在这里，我们研究了青春期父亲吗啡暴露对男性后代吗啡戒断的影响。方法：雄性Wistar大鼠在青春期长期服用吗啡10天。在20天的淘汰期后，成年雄性被允许与未成熟的雌性交配。采用条件场所厌恶法对成年雄性后代进行纳洛酮沉淀吗啡戒断的躯体和情感成分测试。此外，通过细胞外单单位记录，记录了参与阿片类药物依赖发展的外侧副巨细胞核（LPGi）在吗啡刺激剂量下的电活动。结果：与对照的盐碱后代相比，吗啡后代表现出纳洛酮诱导的阿片戒断的躯体和情感体征的增强表达。体内记录显示，在吗啡中毒和盐中毒的动物中，LPGi神经元对急性吗啡给药表现出不同的反应（抑制性、兴奋性和无变化）。吗啡诱导的放电抑制在吗啡后代中增强。但吗啡对放电兴奋的影响程度未达到显著性水平。此外，母体对吗啡遗传后代的行为缺乏改变表明，这是由于表观遗传性状在代间的生殖系依赖传递。结论：孕前父亲在青春期接触吗啡会增强男性后代的阿片戒断症状，这至少部分是通过lgi相关脑回路的表观遗传改变介导的。
Background:Opiate exposure during adolescence perturbs the brain's maturation process and potentially confers long-term adverse consequences, not only in exposed individuals but also in their posterity. Here, we investigate the outcomes of adolescent paternal morphine exposure on morphine withdrawal profile in male offspring.Methods:Male Wistar rats were chronically subjected to 10 days of an escalating regimen of morphine during adolescence. After a 20-day washout period, adult males were allowed to copulate with naive females. The adult male offspring were tested for somatic and affective components of naloxone-precipitated morphine withdrawal using conditioned place aversion. Moreover, electrical activity of the lateral paragigantocellularis (LPGi) nucleus, which is involved in development of opiate dependence, was recorded in response to a challenge dose of morphine via extracellular single-unit recordings.Results:Morphine-sired offspring exhibited augmented expression of naloxone-induced somatic and affective signs of opiate withdrawal compared to the control saline-sired counterparts. In vivo recording revealed that LPGi neurons displayed heterogeneous responses (inhibitory, excitatory, and no change) to acute morphine administration in both morphine- and saline-sired animals. The morphine-induced discharge inhibition was potentiated in morphine-sired offspring. However, the extent of discharge excitation in response to morphine did not reach significance in these subjects. Moreover, the lack of alteration in maternal behavior toward morphine-sired offspring indicates that this is due to germline-dependent transmission of epigenetic traits across generations.Conclusions:Preconception paternal exposure to morphine during adolescence potentiates opiate withdrawal signs in male offspring which is mediated, at least in part, by epigenetic alteration of LPGi-related brain circuitry.