Ghaemi-Jandabi Masoumeh, Azizi Hossein, Ahmadi-Soleimani S Mohammad, Semnanian Saeed
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Brain Res Bull. 2017 Apr;130:107-111. doi: 10.1016/j.brainresbull.2017.01.010. Epub 2017 Jan 16.
Orexin (hypocretin) neuropeptides play a pivotal role in expression of opioid withdrawal signs. Hypothalamic orexinergic neurons provide dense afferents for the nucleus locus coeruleus (LC). Somatic signs of opioid withdrawal are associated with the enhanced activity of LC neurons. In addition, intra-LC administration of orexin-A leads to the hyperactivity of LC neurons. The present study was an attempt to investigate whether intra-LC microinjection of orexin-A induces morphine withdrawal-like signs in both morphine dependent and control rats. To end this, adult male Wistar rats weighing 250-300g were used. For induction of morphine dependence, animals received morphine sulfate subcutaneously (10mg/kg, s.c.) at an interval of 12h for 9days. On day 10, intra-LC orexin injection (100μM, 200nl) was carried out two hours after last morphine administration. Morphine withdrawal-like signs were assessed in a transparent Plexiglas test chamber (30cm diameter, 50cm height) for 25min. Orexin-A microinjection induced some morphine withdrawal-like signs in both morphine dependent (chewing, scratching, rearing, teeth chattering, wet-dog shake and paw tremor) and control (chewing, scratching, rearing, sniffing, wet-dog shake and head tremor) rats. Furthermore, microinjection of SB-334867, a selective orexin type-1 receptor antagonist before orexin-A significantly suppressed orexin-induced morphine withdrawal-like signs. It seems that orexin-A, via increasing the activity of LC neurons, mediates the induction of some morphine withdrawal-like signs independent of morphine dependence.
食欲素（下丘脑泌素）神经肽在阿片类药物戒断症状的表达中起关键作用。下丘脑食欲素能神经元为蓝斑核（LC）提供密集的传入纤维。阿片类药物戒断的躯体症状与LC神经元活性增强有关。此外，向LC内注射食欲素-A会导致LC神经元活动亢进。本研究旨在探讨向LC内微量注射食欲素-A是否会在吗啡依赖大鼠和对照大鼠中诱发类似吗啡戒断的症状。为此，使用了体重250 - 300g的成年雄性Wistar大鼠。为诱导吗啡依赖，动物每隔12小时皮下注射硫酸吗啡（10mg/kg，皮下注射），共9天。在第10天，在最后一次注射吗啡后两小时进行向LC内注射食欲素（100μM，200nl）。在一个透明的有机玻璃测试箱（直径30cm，高50cm）中评估25分钟的类似吗啡戒断症状。向LC内微量注射食欲素-A在吗啡依赖大鼠（咀嚼、抓挠、竖毛、牙齿打颤、湿狗样抖动和爪子震颤）和对照大鼠（咀嚼、抓挠、竖毛、嗅探、湿狗样抖动和头部震颤）中均诱发了一些类似吗啡戒断的症状。此外，在注射食欲素-A之前预先注射选择性食欲素1型受体拮抗剂SB - 334867可显著抑制食欲素诱导的类似吗啡戒断的症状。似乎食欲素-A通过增加LC神经元的活性，介导了一些与吗啡依赖无关的类似吗啡戒断症状的诱发。
