Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
Pharmacol Biochem Behav. 2022 Sep;219:173449. doi: 10.1016/j.pbb.2022.173449. Epub 2022 Aug 13.
This study was done to evaluate the effect of co-treatment of orexin agents along with citalopram on the modulation of depression-like behavior and the expression of BDNF in the prefrontal cortex (PFC) of sleep-deprived male mice. A sleep deprivation model was performed in which rapid eye movement (REM) sleep was completely prohibited, and non-REM sleep was intensely reduced for 24 h. For drug microinjection, the guide cannula was surgically fixed in the left lateral ventricle of mice. Furthermore, we used the open-field test (OFT), forced swim test (FST), tail suspension test (TST), and splash test for recording depression-like behavior as well as Real-Time PCR amplification for assessing the expression of BDNF in the PFC of REM sleep-deprived mice. Our results revealed that REM sleep deprivation did not change locomotor activity while increased depressive-like behavior in FST, TST, and splash tests. However, the expression of BDNF was decreased in the PFC. Intraperitoneally (i.p.) administration of citalopram induced antidepressant effect in the normal and REM sleep-deprived mice. Moreover, intracerebroventricular (i.c.v.) microinjection of a non-effective dose of SB-334867, an orexin antagonist, potentiated the antidepressant-like effect of citalopram. On the other hand, a non-significant dosage of orexin-1 reversed the antidepressant effect of citalopram in the normal and REM sleep-deprived animals. Furthermore, our results showed that injection of citalopram alone or with SB-334867 increased the mRNA expression level of BDNF in the PFC of REM sleep-deprived mice. These data suggest that REM sleep deprivation interferes with the neural systems underlying the depression-like process and supports a likely interaction of the orexin system with citalopram on the modulation of depression-like behavior in REM sleep-deprived mice.
这项研究旨在评估在剥夺 REM 睡眠的雄性小鼠的 PFC 中，同时使用食欲素激动剂和西酞普兰进行治疗对抑郁样行为的调制和 BDNF 表达的影响。REM 睡眠完全被禁止，而非 REM 睡眠强烈减少 24 小时，进行了睡眠剥夺模型。为了进行药物微注射，将引导套管手术固定在小鼠的左侧脑室中。此外，我们使用了旷场测试（OFT）、强迫游泳测试（FST）、悬尾测试（TST）和飞溅测试来记录抑郁样行为，以及使用 Real-Time PCR 扩增来评估 REM 睡眠剥夺小鼠 PFC 中 BDNF 的表达。我们的结果表明，REM 睡眠剥夺不会改变运动活性，而在 FST、TST 和飞溅测试中增加了抑郁样行为。然而，BDNF 的表达在 PFC 中减少。西酞普兰的腹腔内（i.p.）给药在正常和 REM 睡眠剥夺的小鼠中诱导了抗抑郁作用。此外，脑室（i.c.v.）微注射非有效剂量的 SB-334867，一种食欲素拮抗剂，增强了西酞普兰的抗抑郁样作用。另一方面，非有效剂量的食欲素-1 逆转了正常和 REM 睡眠剥夺动物中西酞普兰的抗抑郁作用。此外，我们的结果表明，单独注射西酞普兰或与 SB-334867 一起注射，增加了 REM 睡眠剥夺小鼠 PFC 中 BDNF 的 mRNA 表达水平。这些数据表明，REM 睡眠剥夺干扰了抑郁样过程的神经系统，并支持食欲素系统与 REM 睡眠剥夺小鼠中西酞普兰对抑郁样行为的调制之间可能存在相互作用。
