McCormick C M, Merrick A, Secen J, Helmreich D L
Neuroscience Program, Brock University, St Catharines, Ontario, Canada.
J Neuroendocrinol. 2007 Feb;19(2):116-26. doi: 10.1111/j.1365-2826.2006.01515.x.
There has been little research on effects of chronic stressors on neuroendocrine function in adolescence despite increasing evidence of enduring effects of stressors during this period on behaviour in adulthood. We previously reported that social stress (SS: daily 1 h isolation and new cage partner for 16 days) in adolescence altered locomotor responses to psychostimulants in adulthood. Here, we investigated neuroendocrine responses over the duration of the procedure that may underlie the enduring effects of SS. SS rats were compared to rats undergoing daily isolation only (ISO) and controls (CTL) to determine responses to acute and repeated isolation with and without social instability. At 30 days of age (first isolation), higher plasma corticosterone and corticotrophin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus and in the central nucleus of the amygdala (CeA) were found in males caged with a new partner (SS) after isolation than those returned to their original partner (ISO). On day 45, SS males and females showed less habituation (higher bioactive levels of corticosterone based on plasma corticosterone and corticosteroid binding globulin levels) to the 16th episode of isolation than did ISO. SS and ISO had higher baseline expression of CRH mRNA in the PVN on day 45 than did CTL, and only CTL had increased levels after isolation. CRH mRNA expression in the CeA increased to a first isolation in CTL and to a 16th isolation in SS but not in ISO males. Modest differences in social interactions were observed between SS and ISO when returned to their cages after isolation. The results suggest that mild social stressors in adolescence impede neuroendocrine adaptation to homotypic stressors. The resultant increase in exposure to glucocorticoids over adolescence may alter ongoing brain development and increase vulnerability to psychopathology.
尽管越来越多的证据表明，这一时期的应激源对成年期行为有持久影响，但关于慢性应激源对青少年神经内分泌功能影响的研究却很少。我们之前报道过，青少年时期的社会应激（SS：每天隔离1小时并更换新笼伴，持续16天）会改变成年期对精神兴奋剂的运动反应。在此，我们研究了该过程持续期间的神经内分泌反应，这些反应可能是SS持久影响的基础。将SS大鼠与仅接受每日隔离的大鼠（ISO）和对照组（CTL）进行比较，以确定在有或没有社会不稳定因素的情况下，对急性和反复隔离的反应。在30日龄（首次隔离）时，与回到原笼伴的大鼠（ISO）相比，与新笼伴关在一起的雄性大鼠（SS）在隔离后，下丘脑室旁核（PVN）和杏仁核中央核（CeA）中血浆皮质酮和促肾上腺皮质激素释放激素（CRH）mRNA表达更高。在第45天，与ISO相比，SS雄性和雌性对第16次隔离的适应性较差（基于血浆皮质酮和皮质类固醇结合球蛋白水平，皮质酮的生物活性水平更高）。在第45天，SS和ISO的PVN中CRH mRNA的基线表达高于CTL，且只有CTL在隔离后水平升高。CeA中CRH mRNA表达在CTL中首次隔离时增加，在SS中第16次隔离时增加，但在ISO雄性大鼠中未增加。隔离后回到笼中时，观察到SS和ISO之间在社交互动上有适度差异。结果表明，青少年时期的轻度社会应激源会阻碍神经内分泌对同型应激源的适应。青春期糖皮质激素暴露的增加可能会改变正在进行的大脑发育，并增加患精神病理学疾病的易感性。
