Modanifil activates the histaminergic system through the orexinergic neurons
Modanifil activates the histaminergic system through the orexinergic neurons
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DOI：
10.1016/j.neulet.2010.08.005
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发表时间：
2010-10-15
影响因子：
2.5
通讯作者：
Yamatodani, Atsushi
中科院分区：
文献类型：
--
作者：
Ishizuka, Tomoko;Murotani, Tomotaka;Yamatodani, Atsushi
莫达非尼是一种用于治疗嗜睡症的药物。我们以前报道，莫达非尼增加大鼠下丘脑组胺释放，但没有增加组胺耗竭小鼠的自发活动，表明莫达非尼诱导的自发活动涉及组胺能系统莫达非尼也被认为是通过食欲素能神经元表达其作用，食欲素增加下丘脑组胺释放。这些研究结果使我们调查莫达非尼是否通过食欲素能系统激活组胺能系统。在本研究中，我们进行了体内微透析和c-Fos免疫组织化学研究食欲素能系统是否介导莫达非尼使用食欲素神经元缺陷小鼠激活组胺能系统。注射后2小时，莫达非尼（150 mg/kg）引起野生型小鼠组胺释放的显著增加，但莫达非尼对食欲素神经元缺陷小鼠组胺释放无影响。免疫组织化学研究发现，在食欲素能神经元缺陷小鼠的结节乳头核中，组胺能神经元的胞体仅存在于该核中，而没有神经元的激活。这些结果表明，莫达非尼诱导的组胺释放增加需要完整的食欲素能神经元。(C)2010爱思唯尔爱尔兰有限公司版权所有
Modafinil is a drug used to treat hypersomnolence of narcolepsy. We previously reported that modafinil increases hypothalamic histamine release in rats but did not increase locomotor activity in histamine-depleted mice, suggesting that modafinil-induced locomotor activity involves the histaminergic system Modafinil is also thought to express its effect through the orexinergic neurons, and orexin increases hypothalamic histamine release. These findings led us to investigate whether modafinil activates the histaminergic system via the orexinergic system In the present study, we performed in vivo microdialysis and c-Fos immunohistochemistry to investigate whether the orexinergic system mediates the activation of the histaminergic system by modafinil using orexin neuron-deficient mice. Two hours after the injection, modafinil (150 mg/kg) caused a significant increase of histamine release compared to the basal release in wild type mice However, modafinil had no effect on the histamine release in orexin neuron-deficient mice. By immunohistochemical study, we found that there was no neuronal activation in the tuberomammillary nucleus where the cell bodies of the histaminergic neurons exclusively exist in orexin neuron-deficient mice These findings indicate that modafinil-induced increment of histamine release requires intact orexinergic neurons. (C) 2010 Elsevier Ireland Ltd. All rights reserved