Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Neurobiology, University of Massachusetts Medical School, Worcester, USA.
J Psychopharmacol. 2020 Nov;34(11):1289-1299. doi: 10.1177/0269881120953993. Epub 2020 Oct 8.
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.
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 naïve 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.
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.
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.
青春期接触阿片类药物会干扰大脑的成熟过程，并可能带来长期的不良后果，不仅在暴露个体中，而且在他们的后代中也是如此。在这里，我们研究了青春期父代吗啡暴露对雄性后代吗啡戒断特征的影响。
雄性 Wistar 大鼠在青春期接受 10 天递增剂量的吗啡慢性处理。经过 20 天的洗脱期后，成年雄性大鼠被允许与未交配的雌性大鼠交配。成年雄性后代通过条件性位置厌恶测试来检测纳洛酮引发的吗啡戒断的躯体和情感成分。此外，通过细胞外单细胞记录，记录外侧巨细胞旁核（LPGi）的电活动，该核参与阿片类药物依赖的发展，以响应挑战剂量的吗啡。
与对照生理盐水生育的对照组相比，吗啡生育的后代表现出纳洛酮诱导的阿片类戒断躯体和情感迹象的表达增强。体内记录显示，在吗啡和生理盐水生育的动物中，LPGi 神经元对急性吗啡给药表现出异质反应（抑制、兴奋和无变化）。吗啡生育的后代中，LPGi 神经元对吗啡诱导的放电抑制增强。然而，这些个体对吗啡的放电兴奋程度没有达到显著水平。此外，母亲对吗啡生育的后代的行为没有改变表明，这是由于代际间通过种系传递的表观遗传特征所致。
青春期父代暴露于吗啡会增强雄性后代的阿片戒断迹象，这至少部分是通过 LPGi 相关脑回路的表观遗传改变介导的。
