Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine
Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine
复制标题
DOI：
10.1523/jneurosci.2761-05.2006
复制
发表时间：
2006-01-11
影响因子：
5.3
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Narita, M;Nagumo, Y;Suzuki, T
在这项研究中，我们研究了啮齿动物中食欲素能系统在 mu-阿片受体激动剂吗啡诱导的多巴胺相关行为中的作用。在小鼠腹侧被盖区（VTA）观察到酪氨酸羟化酶与食欲素受体的广泛共表达。将食欲素 A 和食欲素 B 显着注射到 VTA 中，伏隔核中多巴胺及其主要代谢物的水平显着增加。在野生型小鼠中观察到的皮下吗啡诱导的位置偏好和过度运动在缺乏前食欲素原基因的小鼠中被消除。 VTA内注射选择性食欲素受体拮抗剂SB334867A [1-(2-甲基苯并恶唑-6-基)-3-[1.5]萘啶-4-基脲]显着抑制吗啡诱导的大鼠位置偏好。此外，通过删除前食欲素原基因，小鼠大脑中吗啡产生的透析液多巴胺水平显着降低。这些发现提供了新的证据，证明 VTA 中含有食欲素的神经元直接参与吗啡通过激活啮齿动物中脑边缘多巴胺通路而诱导的奖赏效应和过度运动。
In this study, we investigated the role of orexinergic systems in dopamine-related behaviors induced by the mu-opioid receptor agonist morphine in rodents. Extensive coexpression of tyrosine hydroxylase with orexin receptors was observed in the mouse ventral tegmental area (VTA). The levels of dopamine and its major metabolites in the nucleus accumbens were markedly increased by the microinjection of orexin A and orexin B into the VTA. The subcutaneous morphine-induced place preference and hyperlocomotion observed in wild-type mice were abolished in mice that lacked the prepro-orexin gene. An intra-VTA injection of a selective orexin receptor antagonist SB334867A [1-(2-methylbenzoxazol-6-yl)-3-[1.5]naphthyridin-4-yl urea] significantly suppressed the morphine-induced place preference in rats. Furthermore, the increased level of dialysate dopamine produced by morphine in the mouse brain was significantly decreased by deletion of the prepro-orexin gene. These findings provide new evidence that orexin-containing neurons in the VTA are directly implicated in the rewarding effect and hyperlocomotion induced by morphine through activation of the mesolimbic dopamine pathway in rodents.