Sex- and Age-dependent Effects of Orexin 1 Receptor Blockade on Open-Field Behavior and Neuronal Activity.
Sex- and Age-dependent Effects of Orexin 1 Receptor Blockade on Open-Field Behavior and Neuronal Activity.
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DOI：
10.1016/j.neuroscience.2018.04.005
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发表时间：
2018-06-15
期刊：
影响因子：
3.3
通讯作者：
Bhatnagar S
中科院分区：
文献类型：
--
作者：
Blume SR;Nam H;Luz S;Bangasser DA;Bhatnagar S
青春期是大脑发育的敏感和关键时期，焦虑、抑郁和创伤后应激障碍等精神疾病更容易在压力性生活事件后出现。女性患精神疾病的可能性是男性的两倍。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、觉醒和下丘脑-垂体-肾上腺轴活动的重要神经肽。在青春期或成年期，食欲素在调节雄性和雌性大鼠的唤醒行为中的作用知之甚少。在这里，我们研究了SB 334867对青春期早期（PND 31-33）或成年期（PND 75-77）雄性和雌性大鼠旷场行为的影响。动物注射0（溶剂）、1、10或30 mg/kg SB 334867（i. p.）。30分钟后，他们被放置在一个开放的领域，行为和神经元活动（c-Fos）进行了评估。在青春期雄性中，与溶媒组相比，SB 334867显著增加了10 mg/kg组的不动性。然而，在青春期女性中没有观察到青春期男性不动性的增加。与青春期雄性动物相反，10 mg/kg剂量组的成年雄性动物显示出与溶剂组相反的不动性效应。这些结果表明，10 mg/kg剂量的SB 334867在青少年和成年雄性中具有相反的作用，但在青少年和成年雌性中几乎没有作用。边缘系统区域之间的功能网络的差异可能是食欲素受体阻滞剂对大鼠性别和年龄依赖性影响的基础。
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.
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