Khedr Lobna H, Nassar Noha N, El-Denshary Ezzeldin S, Abdel-Tawab Ahmed M
Department of Pharmacology, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Neuropsychiatr Dis Treat. 2015 Nov 13;11:2887-901. doi: 10.2147/NDT.S87089. eCollection 2015.
The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS) model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX) in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally). Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT) was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c), caspase-3 (Casp-3), as well as nitric oxide metabolites (NOx) were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001) as well as the changes in adenos-ine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001). Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression.
应激诱导抑郁症的分子机制尚未完全阐明。因此，本研究旨在测试慢性轻度应激（CMS）模型中的行为变化与海马能量代谢变化之间的联系，以及帕罗西汀（PAROX）在改善这些变化中的作用。将雄性Wistar大鼠分为三组：溶剂对照组、暴露于CMS的大鼠组和接受PAROX（10mg/kg/天腹腔注射）的暴露于CMS的大鼠组。进行了蔗糖偏好试验、旷场试验和强迫游泳试验。检测血清中的皮质酮（CORT），同时检测海马组织匀浆中的三磷酸腺苷及其代谢产物、胞质细胞色素c（Cyt-c）、半胱天冬酶-3（Casp-3）以及一氧化氮代谢产物（NOx）。与对照组相比，暴露于CMS的大鼠蔗糖偏好和体重下降，而PAROX可使其逆转。PAROX还进一步改善了CMS诱导的血清CORT升高（91.71±1.77 ng/mL对124.5±4.44 ng/mL，P<0.001）以及三磷酸腺苷/二磷酸腺苷的变化（3.76±0.02 nmol/mg蛋白对1.07±0.01 nmol/mg蛋白，P<0.001）。此外，PAROX降低了Cyt-c和Casp-3的表达，并恢复了NOx水平。本研究强调了PAROX在逆转抑郁症CMS模型中与应激诱导的细胞凋亡和海马能量代谢变化相关的抑郁行为中的作用。
