School of Psychological Sciences, Macquarie University, North Ryde, NSW, 2109, Australia.
School of Psychology, University of Sydney, Camperdown, NSW, 2006, Australia.
Neuropsychopharmacology. 2022 Jul;47(8):1561-1573. doi: 10.1038/s41386-022-01336-y. Epub 2022 May 17.
Early life stress (ELS) is associated with perturbed neural development and augmented vulnerability to mental health disorders, including addiction. How ELS changes the brain to increase addiction risk is poorly understood, and there are no therapies which target this ELS-induced vulnerability. ELS disrupts the oxytocin system, which can modulate addiction susceptibility, suggesting that targeting the oxytocin system may be therapeutic in this ELS-addiction comorbidity. Therefore, we determined whether adolescent oxytocin treatment after ELS could: (1) reduce vulnerability to anxiety, social deficits, and methamphetamine-taking and reinstatement; and (2) restore hypothalamic oxytocin and corticotropin-releasing factor expressing neurons and peripheral oxytocin and corticosterone levels. Long Evans pups underwent maternal separation (MS) for either 15 min or 360 min on postnatal days (PND) 1-21. During adolescence (PNDs 28-42), rats received a daily injection of either oxytocin or saline. In Experiment 1, adult rats were assessed using the elevated plus-maze, social interaction procedure, and methamphetamine self-administration procedure, including extinction, and cue-, methamphetamine- and yohimbine-induced reinstatement. In Experiment 2, plasma for enzyme immunoassays and brain tissue for immunofluorescence were collected from adult rats after acute stress exposure. Adolescent oxytocin treatment ameliorated ELS-induced anxiety and reduced methamphetamine- and yohimbine-induced reinstatement in both sexes, and suppressed methamphetamine intake and facilitated extinction in males only. Additionally, adolescent oxytocin treatment after ELS restored oxytocin-immunoreactive cells and stress-induced oxytocin levels in males, and attenuated stress-induced corticosterone levels in both sexes. Adolescent oxytocin treatment reverses some of the ELS effects on later-life psychopathology and vulnerability to addiction.
早期生活应激（ELS）与神经发育障碍和精神健康障碍（包括成瘾）易感性增加有关。ELS 如何改变大脑增加成瘾风险还知之甚少，也没有针对这种 ELS 诱导易感性的治疗方法。ELS 破坏了催产素系统，催产素系统可以调节成瘾易感性，这表明靶向催产素系统可能是治疗 ELS-成瘾共病的一种方法。因此，我们确定青春期 ELS 后给予催产素治疗是否可以：(1)降低焦虑、社交缺陷和甲基苯丙胺摄入及复吸的易感性；(2)恢复下丘脑催产素和促肾上腺皮质释放因子表达神经元及外周催产素和皮质酮水平。长爪沙鼠在出生后第 1-21 天接受 15 分钟或 360 分钟的母婴分离（MS）。在青春期（PND 28-42），大鼠每天接受催产素或生理盐水注射。在实验 1 中，成年大鼠进行高架十字迷宫、社交互动程序和甲基苯丙胺自我给药程序评估，包括消退、线索、甲基苯丙胺和育亨宾诱导的复吸。在实验 2 中，急性应激暴露后从成年大鼠采集血浆用于酶免疫测定，采集脑组织用于免疫荧光检测。青春期 ELS 后给予催产素治疗可改善焦虑，并降低雌雄大鼠的甲基苯丙胺和育亨宾诱导的复吸，抑制雄性大鼠的甲基苯丙胺摄入并促进其消退。此外，青春期 ELS 后给予催产素治疗可恢复雄性大鼠的催产素免疫反应细胞和应激诱导的催产素水平，并降低雌雄大鼠的应激诱导皮质酮水平。青春期 ELS 后给予催产素治疗可逆转 ELS 对成年后精神病理学和成瘾易感性的一些影响。
Zotero 插件
