Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran.
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Neuropeptides. 2014 Jun;48(3):179-85. doi: 10.1016/j.npep.2014.04.003. Epub 2014 Apr 21.
The orexins (hypocretins) are lateral hypothalamic (LH) neuropeptides that have been implicated in a variety of behaviors ranging from feeding to sleep and arousal. Evidence from animal models suggests a role for orexins in reward processing and drug addiction. In the present study, we investigated the direct effect of an orexin antagonist in the ventral tegmental area (VTA) on acquisition and expression of morphine conditioned place preference (CPP) induced by concurrent stimulation of the LH. Eighty-one adult male Wistar rats weighing 220-280 g were unilaterally implanted by two separate cannulae into the LH and VTA. The CPP paradigm was done; conditioning score and locomotor activity were recorded by Ethovision software. The animals received SB334867 as a selective orexin-1 receptor antagonist (0.1, 1 and 10 nmol/0.3 μl DMSO) in the VTA, just 5 min prior to intra-LH administration of ineffective dose of carbachol as a cholinergic agonist (62.5 nmol/0.5 μl saline) that stimulates orexin neurons in the LH and ineffective dose of morphine (1 mg/kg, subcutaneously) concurrently during conditioning phase (acquisition experiments) or post-conditioning phase (expression experiments). Data showed that the blockade of orexin-1 receptors in the VTA could inhibit the acquisition (development) but not expression of LH stimulation-induced morphine CPP in the rats. Our findings suggest that the orexinergic projections from the LH to the VTA are involved in the development of the LH stimulation-induced potentiation of morphine rewarding properties and orexin-1 receptors in the VTA have a substantial role in this phenomenon.
食欲素（下丘脑分泌素）是一种侧下丘脑（LH）神经肽，与从进食到睡眠和觉醒等各种行为有关。动物模型的证据表明，食欲素在奖励处理和药物成瘾中起作用。在本研究中，我们研究了腹侧被盖区（VTA）中一种食欲素拮抗剂对 LH 同时刺激诱导的吗啡条件位置偏爱（CPP）的获得和表达的直接影响。81 只成年雄性 Wistar 大鼠，体重 220-280g，通过两个单独的套管单侧植入 LH 和 VTA。进行 CPP 范式；通过 Ethovision 软件记录条件评分和运动活动。动物接受 SB334867，作为选择性食欲素-1 受体拮抗剂（0.1、1 和 10nmol/0.3μl DMSO），在 LH 内给予无效剂量的 carbachol（作为一种刺激 LH 中的食欲素神经元的胆碱能激动剂，62.5nmol/0.5μl 盐水）和无效剂量的吗啡（1mg/kg，皮下）同时在条件期（获得实验）或后条件期（表达实验）进行。数据表明，VTA 中食欲素-1 受体的阻断可以抑制 LH 刺激诱导的吗啡 CPP 的获得（发展），但不能抑制其表达。我们的发现表明，来自 LH 的食欲素投射到 VTA 参与了 LH 刺激诱导的吗啡奖赏特性的增强的发展，并且 VTA 中的食欲素-1 受体在这种现象中起重要作用。
