Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Institute for cognitive Science Studies, Tehran, Iran.
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Neuropeptides. 2017 Dec;66:45-51. doi: 10.1016/j.npep.2017.08.003. Epub 2017 Sep 4.
The orexins are hypothalamic neuropeptides and their role in reward processing and drug addiction has been demonstrated. The extent of involvement of each orexin receptor in the acquisition and expression of conditioned place preference (CPP) for morphine is still a matter of controversy. We investigated the functional differences between orexin-1 and -2 receptor blockade in the ventral tegmental area (VTA) on the acquisition and expression of morphine CPP. A total of 86 adult male Wistar rats weighing 250±30g (age 7-8weeks) received intra-VTA microinjection of either SB334867 (0.1, 1 and 10nM), a selective orexin-1 receptor (OX1R) antagonist, or TCS-OX2-29 (1, 5 and 25nM), a selective orexin-2 receptor (OX2R) antagonist. To measure the acquisition, the animals received each antagonist (SB334867 or TCS-OX2-29) 5min prior to subcutaneous injection of morphine (5mg/kg) during the conditioning phase. To measure the CPP expression, the animals received each antagonist on the post-conditioning phase. The CPP conditioning score was recorded by Ethovision software. Data showed that intra-VTA microinjection of OX1-R antagonist significantly attenuated morphine CPP acquisition, during the conditioning phase, and expression, during the post-conditioning phase. Intra-VTA microinjection of OX2-R antagonist also significantly attenuated morphine CPP acquisition and expression in the mentioned phases. Our results showed the orexin role in learning and memory and indicate that orexin receptors (OX1R and OX2R) function in the VTA is essential for both acquisition and expression of morphine reward in rats in the CPP model.
食欲素是下丘脑神经肽，其在奖励处理和药物成瘾中的作用已得到证实。每个食欲素受体在获得和表达吗啡条件性位置偏爱（CPP）中的参与程度仍存在争议。我们研究了腹侧被盖区（VTA）中食欲素-1 和 -2 受体阻断对吗啡 CPP 获得和表达的功能差异。总共 86 只成年雄性 Wistar 大鼠（体重 250±30g，年龄 7-8 周）接受 VTA 内微量注射 SB334867（0.1、1 和 10nM），一种选择性食欲素-1 受体（OX1R）拮抗剂，或 TCS-OX2-29（1、5 和 25nM），一种选择性食欲素-2 受体（OX2R）拮抗剂。为了测量获得，动物在条件期接受每个拮抗剂（SB334867 或 TCS-OX2-29），然后进行皮下注射吗啡（5mg/kg）。为了测量 CPP 表达，动物在后条件期接受每个拮抗剂。CPP Conditioning 评分通过 Ethovision 软件记录。数据显示，VTA 内微量注射 OX1-R 拮抗剂可显著减弱吗啡 CPP 的获得，在条件期和表达，在条件期后。VTA 内微量注射 OX2-R 拮抗剂也显著减弱了吗啡 CPP 的获得和表达在所述各相中。我们的结果表明食欲素在学习和记忆中的作用，并表明食欲素受体（OX1R 和 OX2R）在 VTA 中的功能对于大鼠 CPP 模型中吗啡奖励的获得和表达都是必不可少的。
