Shahidi Siamak, Hashemi-Firouzi Nasrin
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Neurosci Lett. 2014 Aug 22;578:27-32. doi: 10.1016/j.neulet.2014.06.027. Epub 2014 Jun 19.
Withdrawal from opioids leads to the expression of aversion behaviors. Previous studies have shown that the serotonergic system has an important role in morphine withdrawal syndrome. The 5-HT7 receptor is a recently discovered member of the 5-HT receptor family that has been shown to be involved in these behaviors. The aim of the present study was to test the role of the 5-HT7 receptor in withdrawal syndrome in morphine-dependent mice with AS19 and SB269970, a selective agonist and antagonist of this receptor, respectively. Dependence was induced by the repeated administration of morphine for five consecutive days. The morphine-dependent mice received AS19 (3, 5, or 10mg/kg, intraperitoneal) or SB269970 (1, 3, or 10mg/kg, intraperitoneal) 15 min prior to the precipitation of morphine withdrawal syndromes by naloxone (3mg/kg, subcutaneous). Withdrawal symptoms, including percent weight loss, jumping, teeth chattering, writhing, body and face grooming, sniffing, standing, and head and limb shaking, were recorded for 30 min after the naloxone injection. The morphine-dependent mice had significantly more withdrawal symptoms than naive control mice. The administration of AS19 reduced most of the morphine withdrawal symptoms. However, SB2699 increased some of the withdrawal symptoms, including teeth chattering, face grooming, jumping, and head and limb shaking. These findings suggest that the 5-HT7 receptor is involved in morphine withdrawal. Its activation decreased and its inactivation increased the morphine withdrawal syndrome. Further studies are recommended to better understand the role of the 5-HT7 receptor in morphine dependence and withdrawal.
停用阿片类药物会导致厌恶行为的表现。先前的研究表明，血清素能系统在吗啡戒断综合征中起重要作用。5-HT7受体是最近发现的5-HT受体家族成员，已被证明与这些行为有关。本研究的目的是分别用该受体的选择性激动剂AS19和拮抗剂SB269970来测试5-HT7受体在吗啡依赖小鼠戒断综合征中的作用。通过连续五天重复给予吗啡诱导依赖性。在通过纳洛酮（3mg/kg，皮下注射）诱发吗啡戒断综合征前15分钟，给吗啡依赖小鼠腹腔注射AS19（3、5或10mg/kg）或SB269970（1、3或10mg/kg）。在注射纳洛酮后30分钟记录戒断症状，包括体重减轻百分比、跳跃、牙齿打颤、扭体、身体和面部梳理、嗅闻、站立以及头部和肢体颤抖。吗啡依赖小鼠的戒断症状明显多于未处理的对照小鼠。给予AS19可减轻大多数吗啡戒断症状。然而，SB2699增加了一些戒断症状，包括牙齿打颤、面部梳理、跳跃以及头部和肢体颤抖。这些发现表明5-HT7受体参与吗啡戒断。其激活可减轻而失活会加重吗啡戒断综合征。建议进一步研究以更好地了解5-HT7受体在吗啡依赖和戒断中的作用。
