Strain differences in maternal neuroendocrine and behavioral responses to stress and the relation to offspring cocaine responsiveness
Strain differences in maternal neuroendocrine and behavioral responses to stress and the relation to offspring cocaine responsiveness
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DOI：
10.1016/j.ijdevneu.2019.06.009
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发表时间：
2019-11-01
影响因子：
1.8
通讯作者：
Kippin, Tod E.
中科院分区：
文献类型：
--
作者：
Bagley, Jared R.;Adams, Julia;Kippin, Tod E.
早期生活压力暴露，包括产前压力（PNS），影响许多疾病的后续风险，包括药物滥用，这些影响与遗传因素相互作用，以确定疾病的风险。我们以前证明了基因X的环境相互作用，在BXD重组近交系小鼠品系面板和它们的祖先品系在可卡因诱导的奖励和运动的PNS调制。关键解剖与PNS的遗传相互作用是考虑压力传递到后代的模式。母体神经内分泌反应在压力和随后的母子互动压力可能作为传输模式的PNS诱导的可卡因反应性的变化。因此，我们的特点是母亲的压力反应，通过测量约束应力诱导的血浆皮质酮（CORT）在妊娠期间，以及约束应力对母鼠-幼鼠接触的影响，在出生后的第一个10天在BXD和祖小鼠品系。束缚应激与应变相互作用，影响血浆CORT水平和母鼠-幼鼠接触，表明母体应激反应的遗传变异。此外，在母体压力反应的应变水平的变化与可卡因的反应表现出的成年后代的影响。这些研究结果涉及多种模式的母体应激反应在后代药物反应性的改变，并表明，在生命早期的母体内分泌和行为反应的评估可以用来解剖复杂的交叉母体因素，后代和遗传学的反应。
Early life stress exposure, including prenatal stress (PNS), influences subsequent risk for many disorders, including substance abuse, and these effects interact with genetic factors to determine risk for disease. We previously demonstrated gene X environmental interactions across the BXD recombinant inbred mouse strain panel and their progenitor strains in PNS modulation of cocaine-induced reward and locomotion. Critical to dissecting genetic interactions with PNS is consideration of the modes of stress transmission to the offspring. Both maternal neuroendocrine responses during stress and subsequent maternal-offspring interactions following stress may serve as transmission modes for PNS-induced changes in cocaine responsiveness. Therefore, we characterized the maternal stress response by measuring restraint stress-induced plasma corticosterone (CORT) during gestation as well as effects of restraint stress on dam-pup contact in the first 10 postnatal days in BXD and progenitor mouse strains. Restraint stress interacted with strain to affect plasma CORT levels and dam-pup contact, indicating heritable variation of the maternal stress response. Furthermore, strain-level variance in maternal stress response correlated to the impact on cocaine response exhibited by adult offspring. These findings implicate multiple modes of maternal stress response in alterations of offspring drug responsiveness and indicate that assessment of maternal endocrine and behavioral responses during early life can be utilized to dissect the complex intersection of maternal factors, the response of the offspring and genetics.