Departamento de Psicobiologia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, 1° andar, São Paulo, SP, 04024-002, Brazil.
Mol Neurobiol. 2021 Mar;58(3):926-943. doi: 10.1007/s12035-020-02164-1. Epub 2020 Oct 15.
Early life stress is considered a risk factor for the development of long-term psychiatric disorders. Maternal deprivation (MD) is a useful paradigm to understand the neurobiological underpinnings of early stress-induced changes in neurodevelopment trajectory. The goal of the present study was to examine the effects of a chronic treatment with escitalopram (ESC) on the hippocampal levels of BDNF and neuropeptide Y (NPY), expression of serotonin type 1A receptor (5-HT), plasma corticosterone levels and emotional behaviours in male and female adolescent rats submitted to MD at 9 days of life (group DEP9) and challenged with a brief and mild stress (saline injection (SAL)) at the end of MD. Whole litters were kept with mothers (CTL) or submitted to MD (DEP9). Within each group, pups were stress-challenged (CTL-SAL and DEP9-SAL) or not (CTL-NSAL and DEP9-NSAL). ESC or vehicle treatments began at weaning and lasted 24 days, when animals were sacrificed for determination of neurobiological variables or submitted to a battery of tests for evaluation of emotional behaviours. The results showed that BDNF levels were higher in SAL-challenged males and in DEP9-SAL females, whereas 5-HT receptor expression was reduced in DEP9 males and in SAL-challenged females. There were no changes in NPY or corticosterone levels. In the forced swim test, SAL-challenged males and DEP9 females displayed less immobility and ESC only increased social motivation in males. The results indicated that neonatal stress led to sex-dependent changes in neurobiology and behaviour and that chronic ESC treatment had minor effects on these parameters.
早期生活压力被认为是长期精神障碍发展的一个风险因素。母体剥夺（MD）是一种有用的范式，可以理解早期应激引起的神经发育轨迹变化的神经生物学基础。本研究的目的是研究慢性使用艾司西酞普兰（ESC）对经历 9 天大鼠期 MD（DEP9 组）并在 MD 结束时接受短暂轻度应激（盐水注射（SAL））挑战的雄性和雌性青春期大鼠海马脑源性神经营养因子（BDNF）和神经肽 Y（NPY）水平、5-羟色胺 1A 型受体（5-HT）表达、血浆皮质酮水平和情绪行为的影响。整个窝仔与母亲（CTL）一起饲养或进行 MD（DEP9）。在每个组中，幼仔都受到应激挑战（CTL-SAL 和 DEP9-SAL）或未受到应激挑战（CTL-NSAL 和 DEP9-NSAL）。ESC 或载体治疗在断奶时开始并持续 24 天，此时动物被处死以确定神经生物学变量或进行一系列情感行为测试。结果表明，SAL 挑战的雄性和 DEP9-SAL 的雌性 BDNF 水平较高，而 5-HT 受体表达在 DEP9 雄性和 SAL 挑战的雌性中降低。NPY 或皮质酮水平没有变化。在强迫游泳试验中，SAL 挑战的雄性和 DEP9 雌性的不动时间减少，ESC 仅增加雄性的社交动机。结果表明，新生期应激导致神经生物学和行为的性别依赖性变化，而慢性 ESC 治疗对这些参数的影响较小。
