Mousavi Yousof, Azizi Hossein, Mirnajafi-Zadeh Javad, Javan Mohammad, Semnanian Saeed
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
Neurosci Lett. 2014 Aug 22;578:90-4. doi: 10.1016/j.neulet.2014.06.038. Epub 2014 Jun 24.
The aim of this study was to evaluate the effects of orexin type-1 receptor (OX1R) antagonism in locus coeruleus (LC) nucleus on the development of morphine physical dependence in rats. Animals were rendered dependent on morphine by subcutaneous (s.c.) administration of morphine sulfate (6, 16, 26, 36, 46, 56 and 66 mg/kg, 2 ml/kg) at set intervals of 24 h for 7 days. Immediately before each morphine administration, the animals received intra-LC administration of SB-334867 (3 mM, 0.2 μl), a selective orexin type-1 receptor antagonist. On day 8, naloxone (3 mg/kg, i.p.) was injected and physical dependence was evaluated for 30 min. Our results showed that administration of OX1R antagonist before each morphine injection significantly decreased somatic signs of naloxone-induced morphine withdrawal syndrome, including defecation, wet-dog shake, diarrhea, jumping, scratching, and teeth chattering. These results suggest that the activation of OX1R in LC nucleus might be involved in the development of morphine dependency.
本研究的目的是评估蓝斑核中1型食欲素受体（OX1R）拮抗作用对大鼠吗啡身体依赖性形成的影响。通过每隔24小时皮下注射硫酸吗啡（6、16、26、36、46、56和66mg/kg，2ml/kg），连续7天使动物对吗啡产生依赖性。在每次注射吗啡前，动物接受蓝斑核内注射选择性1型食欲素受体拮抗剂SB-334867（3mM，0.2μl）。在第8天，腹腔注射纳洛酮（3mg/kg），并在30分钟内评估身体依赖性。我们的结果表明，每次注射吗啡前给予OX1R拮抗剂可显著减轻纳洛酮诱导的吗啡戒断综合征的躯体症状，包括排便、湿狗样抖动、腹泻、跳跃、抓挠和牙齿打颤。这些结果表明，蓝斑核中OX1R的激活可能参与了吗啡依赖性的形成。
