Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Eur J Pharmacol. 2013 May 15;708(1-3):38-43. doi: 10.1016/j.ejphar.2013.03.013. Epub 2013 Mar 23.
This study was done to investigate the effects of opioid and nitrergic systems on depression in an experimental model of cholestasis in mice, since elevated levels of these substances are seen in cholestatic subjects. Bile duct ligated (BDL) and sham-operated mice were forced to swim individually and the immobility time in the last 4 min of the 6 min test was evaluated to determine the effects of cholestasis on depression. To assess the possible involvement of endogenous opioids and nitric oxide (NO), effective and sub-effective doses of naltrexone an antagonist of opioid receptors, and N-nitro-l-arginine methyl ester (L-NAME) a non-specific NO synthase inhibitor, were administrated acutely and chronically to BDL and Sham-operated mice and then their immobility time was measured in forced swimming test (FST). The immobility time significantly decreased after bile-duct ligation. Naltrexone and L-NAME significantly reversed antidepressant like effect of cholestasis. Co-administration of sub-effective doses of naltrexone and L-NAME also reversed antidepressant effect in FST in chronic administration. But acute drug administration did not reverse the anti-depressant effect of cholestasis. We have shown that elevated levels of endogenous opioids and NO in cholestatic mice induce an anti depressant like effect, causing a reduction in the mice immobility time in FST. And the study also showed the predominant effect of opioid system and NO modulation of that in anti-depressant like effect of cholestasis.
本研究旨在探讨胆郁症实验模型中小鼠阿片和氮能系统对抑郁的影响，因为在胆郁症患者中这些物质的水平升高。胆管结扎（BDL）和假手术小鼠被单独强迫游泳，在 6 分钟测试的最后 4 分钟评估不动时间，以确定胆郁症对抑郁的影响。为了评估内源性阿片类物质和一氧化氮（NO）的可能参与，阿片受体拮抗剂纳曲酮和非特异性一氧化氮合酶抑制剂 N-硝基-L-精氨酸甲酯（L-NAME）的有效和亚有效剂量被急性和慢性给予 BDL 和 Sham 操作的小鼠，然后测量它们在强迫游泳测试（FST）中的不动时间。胆管结扎后，不动时间显著降低。纳曲酮和 L-NAME 显著逆转了胆郁症的抗抑郁样作用。在慢性给药时，亚有效剂量的纳曲酮和 L-NAME 的共同给药也逆转了 FST 中的抗抑郁作用。但急性药物给药并未逆转胆郁症的抗抑郁作用。我们已经表明，胆郁症小鼠中内源性阿片类物质和 NO 水平升高会引起抗抑郁样作用，导致 FST 中小鼠不动时间减少。研究还表明，阿片系统在胆郁症的抗抑郁样作用中占主导地位，而 NO 调节了这种作用。
