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首页> 外文期刊>The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics >Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2
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Orexin-A/Hypocretin-1 Mediates Cocaine-Seeking Behavior in the Posterior Paraventricular Nucleus of the Thalamus via Orexin/Hypocretin Receptor-2

机译：Orexin-A / Hypocretin-1通过Orexin / Hypocretin Receptor-2介导丘脑后脑室后核中的可卡因寻找行为。

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摘要

Orexin/hypocretin (Orx/Hcrt) projections from the lateral hypothalamus to the paraventricular nucleus of the thalamus (PVT) are implicated in drug addiction. Specifically, the posterior section of the PVT (pPVT) innervates brain structures that modulate motivated behavior. This study investigated the role of pPVTOrx/Hcrt transmission in cocaine-seeking behavior. Because the effects of Orx/Hcrt are mediated by two Orx/Hcrt receptors (Hcrt-r1 and Hcrt-r2), we examined the extent to which Hcrt-r1 and Hcrt-r2 are involved in Orx/Hcrt-induced cocaine seeking. Male Wistar rats were made cocaine dependent by self-administering cocaine 6 hours/day (long access) for 21 days. After self-administration training, the rats underwent daily extinction training, during which cocaine was withheld. After extinction, the rats were injected into the pPVT with Orx-A/Hcrt-1 (0-2 mu g) alone or, using a single dose of 0.5 mu g, in combination with an Hcrt-r1 antagonist (SB334867; 0-15 mu g) or an Hcrt-r2 antagonist (TCSOX229; 0-15 mu g). Orx-A/Hcrt-1 alone reinstated (primed) cocaine seeking. Unexpectedly, coadministration of Orx-A/Hcrt-1 with SB334867 did not have any effects on OrxA/Hcrt-1-induced reinstatement, whereas when coadministered with Orx-A/Hcrt-1, TCSOX229 prevented cocaine-seeking behavior. These results indicate that Hcrt-r2 in the pPVT mediates the reinstating effect of Orx-A/Hcrt-1 in animals with a history of cocaine dependence and further identify Hcrt-r2 as a possible molecular target that can guide future therapeutic approaches for the prevention of drug-seeking behavior.
机译：从下丘脑外侧到丘脑室旁核（PVT）的食欲素/促胰泌素（Orx / Hcrt）投影与药物成瘾有关。具体而言，PVT（pPVT）的后部神经支配调节动机行为的大脑结构。这项研究调查了pPVTOrx / Hcrt传播在可卡因寻求行为中的作用。因为Orx / Hcrt的作用是由两个Orx / Hcrt受体（Hcrt-r1和Hcrt-r2）介导的，所以我们研究了Hcrt-r1和Hcrt-r2参与Orx / Hcrt诱导的可卡因寻找的程度。雄性Wistar大鼠通过每天6小时/天（长期服用）可卡因持续21天使可卡因依赖。自我管理训练后，大鼠每天进行灭绝训练，在此期间停用可卡因。灭绝后，将大鼠单独Orx-A / Hcrt-1（0-2μg）或单剂量0.5μg与Hcrt-r1拮抗剂（SB334867; 0- 15微克）或Hcrt-r2拮抗剂（TCSOX229; 0-15微克）。单独使用Orx-A / Hcrt-1恢复（启动）可卡因搜寻。出乎意料的是，Orx-A / Hcrt-1与SB334867并用对OrxA / Hcrt-1诱导的恢复没有任何作用，而当与Orx-A / Hcrt-1并用时，TCSOX229阻止了可卡因的寻找行为。这些结果表明，pPVT中的Hcrt-r2介导了具有可卡因依赖史的动物的Orx-A / Hcrt-1的恢复作用，并进一步确定了Hcrt-r2是可能的分子靶标，可以指导未来的预防性治疗方法。寻求毒品的行为。

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