Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Psychology and The Neuroscience Program, Temple University, Philadelphia, PA 19122, USA.
Neuroscience. 2018 Jun 15;381:11-21. doi: 10.1016/j.neuroscience.2018.04.005. Epub 2018 Apr 18.
Adolescence is a sensitive and critical period in brain development where psychiatric disorders such as anxiety, depression and post-traumatic stress disorder are more likely to emerge following a stressful life event. Females are two times more likely to suffer from psychiatric disorders than males. Patients with these disorders show alterations in orexins (also called hypocretins), important neuropeptides that regulate arousal, wakefulness and the hypothalamic-pituitary-adrenal axis activity. Little is known on the role of orexins in mediating arousal behaviors in male and female rats during adolescence or adulthood. Here, we examine the influence of orexin 1 receptor blockade by SB334867 in open-field behavior in male and female rats during early adolescence (PND 31-33) or adulthood (PND 75-77). Animals were injected with 0 (vehicle), 1, 10, or 30 mg/kg SB334867 (i.p.). Thirty minutes later, they were placed in an open field, and behavior and neuronal activity (c-Fos) were assessed. In adolescent males, SB334867 significantly increased immobility in the 10 mg/kg group compared to vehicle. However, this increase in immobility in adolescent males was not observed in adolescent females. In contrast to adolescent males, adult males in the 10 mg/kg dose group showed the opposite effect on immobility compared to vehicle. These results indicate that 10 mg/kg dose of SB334867 has opposing effects in adolescent and adult males, but few effects in adolescent and adult females. Differences in functional networks between limbic regions may underlie these effects of orexin receptor blockade that are sex- and age-dependent in rats.
青春期是大脑发育的敏感和关键时期，在此期间，经历应激性生活事件后，焦虑、抑郁和创伤后应激障碍等精神疾病更有可能出现。女性患精神疾病的可能性是男性的两倍。患有这些疾病的患者表现出食欲素（也称为下丘脑泌素）的改变，食欲素是调节觉醒、清醒和下丘脑-垂体-肾上腺轴活动的重要神经肽。关于食欲素在介导青春期和成年期雄性和雌性大鼠觉醒行为中的作用知之甚少。在这里，我们研究了在青春期（PND 31-33）或成年期（PND 75-77）早期，通过 SB334867 阻断食欲素 1 受体对雄性和雌性大鼠旷场行为的影响。动物被注射 0（载体）、1、10 或 30mg/kg 的 SB334867（ip）。30 分钟后，将它们放入旷场中，评估行为和神经元活性（c-Fos）。在青春期雄性大鼠中，与载体相比，10mg/kg 组的 SB334867 显著增加了不动性。然而，在青春期雌性大鼠中没有观察到这种不动性的增加。与青春期雄性大鼠相反，10mg/kg 剂量组的成年雄性大鼠在不动性方面与载体相比表现出相反的效果。这些结果表明，10mg/kg 剂量的 SB334867 在青春期和成年雄性大鼠中具有相反的作用，但在青春期和成年雌性大鼠中几乎没有作用。边缘区域之间功能网络的差异可能是这些食欲素受体阻断作用在大鼠中具有性别和年龄依赖性的基础。
