Saleh Lobna A, Hamza May, El Gayar Nesreen H, Abd El-Samad Abeer A, Nasr Essam A, Masoud Somaia I
Dept. of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Dept. of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Pharmacol Biochem Behav. 2014 Oct;125:29-39. doi: 10.1016/j.pbb.2014.07.013. Epub 2014 Aug 4.
Prostaglandins (PGs) and nitric oxide (NO) may be involved in the pathophysiology of depression. Since NSAIDs decrease PGs and NO production, they may have an antidepressant effect. The aim of the present work was to explore a possible antidepressant action of ibuprofen in the new model of Bacillus Calmette-Guerin (BCG) induced depression. Mice injected with BCG (10(7) CFU/mouse intraperitoneally) showed an increase in the total immobility time during the forced swim test (FST) and the tail suspension test (TST) and an increase in cerebral PGE2 and NO levels. Fluoxetine administered in drinking water at a dose of 80 mg/l, 5 days before BCG and for 2 more weeks resulted in significant decrease in total immobility time during FST and TST and in cerebral PGE2 and NO levels. Both ibuprofen (200 mg/l) and L-NAME (1 g/l) administered in drinking water 24 h before BCG and for 2 more weeks resulted in decrease in the total immobility time during FST and TST and in cerebral PGE2 and NO levels, which was comparable to fluoxetine's effect. On the other hand, l-arginine administered at a dose of 6 g/l in drinking water together with ibuprofen or fluoxetine reversed their effect on FST, TST and cerebral PGE2 and NO levels. Immunohistochemistry showed a decrease in COX-1 and i-NOS immunoreactivity in the CA1 and CA3 areas of the hippocampus following ibuprofen treatment. These results suggest that ibuprofen may have an antidepressant effect through inhibition of PGE2 and NO production, especially in depression secondary to chronic inflammation.
前列腺素（PGs）和一氧化氮（NO）可能参与抑郁症的病理生理学过程。由于非甾体抗炎药（NSAIDs）会减少PGs和NO的生成，它们可能具有抗抑郁作用。本研究的目的是在卡介苗（BCG）诱导的抑郁症新模型中探索布洛芬可能的抗抑郁作用。注射BCG（10⁷CFU/小鼠腹腔注射）的小鼠在强迫游泳试验（FST）和悬尾试验（TST）中的总不动时间增加，脑内PGE2和NO水平升高。在BCG注射前5天及之后2周，以80 mg/l的剂量将氟西汀添加到饮用水中，可使FST和TST中的总不动时间以及脑内PGE2和NO水平显著降低。在BCG注射前24小时及之后2周，将布洛芬（200 mg/l）和L-硝基精氨酸甲酯（L-NAME，1 g/l）添加到饮用水中，可使FST和TST中的总不动时间以及脑内PGE2和NO水平降低，其效果与氟西汀相当。另一方面，以6 g/l的剂量将L-精氨酸添加到饮用水中，与布洛芬或氟西汀共同给药，可逆转它们对FST、TST以及脑内PGE2和NO水平的影响。免疫组织化学显示，布洛芬治疗后海马体CA1和CA3区域的COX-1和诱导型一氧化氮合酶（i-NOS）免疫反应性降低。这些结果表明，布洛芬可能通过抑制PGE2和NO的生成而具有抗抑郁作用，尤其是在慢性炎症继发的抑郁症中。
