Hooshmandi Mehdi, Hosseinmardi Narges, Janahmadi Mahyar, Khakpai Fatemeh, Rohampour Kambiz, Doostmohammadi Jafar
Neurophysiology Research Center, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurophysiology Research Center, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Pharmacol Biochem Behav. 2017 Jul;158:39-48. doi: 10.1016/j.pbb.2017.06.001. Epub 2017 Jun 3.
Herein the effect of hippocampal orexin type-1 receptors (OX1Rs) blockade on morphine withdrawal syndrome was studied. Animals were made dependent by subcutaneous (s.c.) administration of morphine sulfate (10mg/kg) at an interval of 12h for 9 consecutive days. Thereafter, on day 10, naloxone hydrochloride (1.5mg/kg, i.p.) was injected and the somatic signs of withdrawal syndrome were monitored during a 25-min period. Two groups of animals received bilateral microinjection of either SB-334867, a selective OX1Rs antagonist, (0.5μg/0.5μl), or its vehicle into the dorsal hippocampus immediately before each morphine injection. Other groups of animals were made dependent at first and only received a single microinjection of SB-334867 or vehicle on day 10 before naloxone injection. The results showed that intra-hippocampal microinjection of SB-334867 before each morphine treatment, significantly decreased the signs of morphine withdrawal, including teeth chattering (dependent: 18.5±2.3, SB treated: 5±1, p<0.001), diarrhea (dependent: 8.7±0.6, SB treated: 4.1±0.6, p<0.001), ptosis (dependent: 33.8±3.7, SB treated: 11.6±1.1, p<0.001), and chewing (dependent: 40±2.3, SB treated: 29±2.4, p<0.01). SB-334867 did not attenuate withdrawal syndrome, when it was microinjected as a single dose immediately before naloxone injection. The present results suggest a role for orexin in naloxone-precipitated withdrawal and thus possibly morphine dependence and this effect is, at least in part, via OX1Rs in the dorsal hippocampus.
本文研究了海马1型食欲素受体（OX1Rs）阻断对吗啡戒断综合征的影响。通过连续9天每隔12小时皮下注射硫酸吗啡（10mg/kg）使动物产生依赖性。此后，在第10天，注射盐酸纳洛酮（1.5mg/kg，腹腔注射），并在25分钟内监测戒断综合征的躯体症状。两组动物在每次吗啡注射前立即将选择性OX1Rs拮抗剂SB - 334867（0.5μg/0.5μl）或其溶媒双侧微量注射到背侧海马。其他组动物首先产生依赖性，仅在第10天纳洛酮注射前接受单次SB - 334867或溶媒微量注射。结果显示，每次吗啡治疗前海马内微量注射SB - 334867，可显著减轻吗啡戒断症状，包括牙齿打颤（依赖组：18.5±2.3，SB治疗组：5±1，p<0.001）、腹泻（依赖组：8.7±0.6，SB治疗组：4.1±0.6，p<0.001）、眼睑下垂（依赖组：33.8±3.7，SB治疗组：11.6±1.1，p<0.001）和咀嚼（依赖组：40±2.3，SB治疗组：29±2.4，p<0.
