Kurhe Yeshwant, Mahesh Radhakrishnan
Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan 333031, India.
Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan 333031, India.
Pharmacol Biochem Behav. 2015 Sep;136:107-16. doi: 10.1016/j.pbb.2015.07.004. Epub 2015 Jul 15.
In our earlier study we reported the antidepressant activity of ondansetron in obese mice. The present study investigates the effect of ondansetron on depression and anxiety associated with obesity in experimental mice with biochemical evidences. Male Swiss albino mice were fed with high fat diet (HFD) for 14weeks to induce obesity. Then the subsequent treatment with ondansetron (0.5 and 1mg/kg, p.o.), classical antidepressant escitalopram (ESC) (10mg/kg, p.o.) and vehicle (distilled water 10ml/kg, p.o.) was given once daily for 28days. Behavioral assay for depression including sucrose preference test, forced swim test (FST) and anxiety such as light dark test (LDT) and hole board test (HBT) were performed in obese mice. Furthermore, in biochemical estimations oral glucose tolerance test (OGTT), plasma leptin, insulin, corticosterone, brain oxidative stress marker malonaldehyde (MDA), antioxidant reduced glutathione (GSH) and serotonin assays were performed. Results indicated that HFD fed obese mice showed severe depressive and anxiety-like behaviors. Chronic treatment with ondansetron inhibited the co-morbid depression and anxiety in obese mice by increasing sucrose consumption in sucrose preference test and reducing the immobility time in FST, increasing time and transitions of light chamber in LDT, improving head dip and crossing scores in HBT compared to HFD control mice. Ondansetron in obese mice inhibited glucose sensitivity in OGTT, improved plasma leptin and insulin sensitivity, reversed hypothalamic pituitary adrenal (HPA) axis hyperactivity by reducing the corticosterone concentration, restored brain pro-oxidant/anti-oxidant balance by inhibiting MDA and elevating GSH concentrations and facilitated serotonergic neurotransmission. In conclusion, ondansetron reversed the co-morbid depression and anxiety associated with obesity in experimental mice by attenuating the behavioral and biochemical abnormalities.
在我们早期的研究中，我们报道了昂丹司琼在肥胖小鼠中的抗抑郁活性。本研究通过生化证据，调查昂丹司琼对实验性肥胖小鼠抑郁和焦虑的影响。雄性瑞士白化小鼠喂食高脂肪饮食（HFD）14周以诱导肥胖。然后，随后用昂丹司琼（0.5和1mg/kg，口服）、经典抗抑郁药艾司西酞普兰（ESC）（10mg/kg，口服）和赋形剂（蒸馏水10ml/kg，口服）进行治疗，每天一次，持续28天。对肥胖小鼠进行抑郁行为测定，包括蔗糖偏好试验、强迫游泳试验（FST），以及焦虑测定，如明暗试验（LDT）和洞板试验（HBT）。此外，进行生化评估，包括口服葡萄糖耐量试验（OGTT）、血浆瘦素、胰岛素、皮质酮、脑氧化应激标志物丙二醛（MDA）、抗氧化剂还原型谷胱甘肽（GSH）和血清素测定。结果表明，喂食HFD的肥胖小鼠表现出严重的抑郁和焦虑样行为。与HFD对照小鼠相比，昂丹司琼的慢性治疗通过增加蔗糖偏好试验中的蔗糖消耗量、减少FST中的不动时间、增加LDT中光室的时间和转换次数、改善HBT中的头部浸入和穿越分数，抑制了肥胖小鼠共病的抑郁和焦虑。肥胖小鼠中的昂丹司琼在OGTT中抑制葡萄糖敏感性，改善血浆瘦素和胰岛素敏感性，通过降低皮质酮浓度逆转下丘脑-垂体-肾上腺（HPA）轴的过度活跃，通过抑制MDA和提高GSH浓度恢复脑促氧化剂/抗氧化剂平衡，并促进血清素能神经传递。总之，昂丹司琼通过减轻行为和生化异常，逆转了实验小鼠中与肥胖相关的共病抑郁和焦虑。
