Early life stress (ELS) exposure alters brain development, increasing vulnerability for mental illness in adulthood, including depression. Despite this association, there are no approved pharmacotherapies to protect against the emergence of mental illness resulting from ELS. Recent preclinical work showed that oxytocin (OT) administration in adulthood reduced depressive-like behaviour in male rats with a history of ELS. However, the ability of an OT treatment regime in adolescence, a critical developmental window for the OT system, to prevent the expression of depressive-like behaviours following ELS has not been investigated. Therefore, the present study aimed to determine whether chronic OT administration can ameliorate the enduring effects of ELS on depressive-like behaviours in both male and female rats. Following birth, Long Evans rat pups (N = 107) underwent maternal separation (MS) for either 15 min (MS15) or 6 h (MS360) on postnatal days (PND) 1–21. During adolescence (PND 28–42), rats received a daily injection of either OT (1 mg/kg) or saline. During adulthood (PND 57 onwards), effort-related motivation was measured using a model of effortful choice (EC), while behavioural despair was measured using the forced swim test (FST). Lastly, body and organ weights were measured to examine the physiological impacts of ELS and chronic OT administration. Overall, in both sexes, MS360 increased behavioural despair yet had no impact on effort-related motivation. Importantly, adolescent OT administration prevented the MS360-induced increase in behavioural despair in both males and females. Additionally, MS360 resulted in persistent reductions in body weight in both sexes post-weaning and increased spleen weight in males and adrenal weight in females. OT treatment had no impact on body weight in either sex, but prevented the MS-induced increase in adrenal gland weight in females. Overall, these findings have important implications for using oxytocin as a preventative pharmacotherapy after ELS.

早期生活压力 (ELS) 暴露会改变大脑发育，增加成年后患精神疾病（包括抑郁症）的可能性。尽管存在这种关联，但还没有经过批准的药物疗法来预防 ELS 导致的精神疾病的出现。最近的临床前研究表明，在成年期给予催产素 (OT) 可减少具有 ELS 病史的雄性大鼠的抑郁样行为。然而，青春期 OT 治疗方案（OT 系统的关键发育窗口）预防 ELS 后抑郁样行为表达的能力尚未得到研究。因此，本研究旨在确定慢性 OT 给药是否可以改善 ELS 对雄性和雌性大鼠抑郁样行为的持久影响。出生后，Long Evans 幼鼠 (否 = 107) 在产后第 1-21 天 (PND) 接受母体分离 (MS) 15 分钟 (MS15) 或 6 小时 (MS360)。在青春期 (PND 28–42)，大鼠每天接受 OT (1 mg/kg) 或生理盐水注射。在成年期间（PND 57 以后），使用努力选择 (EC) 模型测量与努力相关的动机，而使用强迫游泳测试 (FST) 测量行为绝望。最后，测量体重和器官重量以检查 ELS 和慢性 OT 管理的生理影响。总体而言，MS360 增加了两性的行为绝望，但对与努力相关的动机没有影响。重要的是，青少年 OT 管理阻止了 MS360 引起的男性和女性行为绝望的增加。此外，MS360 导致两性断奶后体重持续下降，雄性脾脏重量增加，雌性肾上腺重量增加。OT 治疗对两种性别的体重都没有影响，但阻止了 MS 引起的女性肾上腺重量增加。总体而言，这些发现对于使用催产素作为 ELS 后的预防性药物疗法具有重要意义。