Orexins-A (OrxA) and -B (OrxB) neuropeptides are synthesized by a group of neurons located in the lateral hypothalamus and adjacent perifornical area, which send their projections to the mesolimbic dopaminergic (DAergic) system including ventral tegmental area and nucleus accumbens (NAc), where orexin receptors are expressed. NAc plays a central role in reward-seeking behavior and drug abuse. NAc-neurons express dopamine-1 (D1R) and dopamine-2 (D2R) receptors. Orexins bind to their two cognate G-protein-coupled receptors, orexin-receptor type-1 (Orx₁R) and type-2 (Orx₂R). Orexin receptor signaling is involved in behaviors such as motivation and addiction. Orexin-containing neurons modulate DAergic activity that is key in synaptic plasticity induced by addictive drugs. However, the effect of OrxA on expression and content of DAergic receptors in NAc is unknown. The purpose of this study was to investigate whether OrxA can alter gene expression and protein levels of D1R/D2R in NAc. Gene expression was evaluated by real-time PCR analysis and protein levels by western blot in rats. The results show that intracerebroventricular (i.c.v.) injection of OrxA increases both gene transcription and protein content of D2R but fails to modify D1R. This effect was also confirmed with OrxA infusion in NAc/Shell. Our results demonstrate for the first time that OrxA induces up-regulation of gene and protein of D2R in NAc. These findings support the hypothesis that OrxA modulates the DAergic transmission and this may serve to understand how orexin signaling enhances DA responses at baseline conditions and in response to psychostimulants.

Orexins-A（OrxA）和-B（OrxB）神经肽是由位于下丘脑外侧和邻近穿孔周围区域的一组神经元合成的，这些神经元将其投影发送到中腹缘多巴胺能（DAergic）系统，包括腹侧被盖区和伏隔核（ NAc），其中表达orexin受体。NAc在寻求奖励的行为和药物滥用中起着核心作用。NAc神经元表达多巴胺1（D1R）和多巴胺2（D2R）受体。Orexins与它们的两个同源G蛋白偶联受体结合，即Orexin受体1型（Orx ₁ R）和2型（Orx ₂R）。食欲素受体信号传导参与诸如动机和成瘾的行为。含食欲素的神经元调节DAergic活动，这是成瘾药物诱导的突触可塑性的关键。但是，OrxA对NAc中DAergic受体的表达和含量的影响尚不清楚。这项研究的目的是调查OrxA是否可以改变NAc中D1R / D2R的基因表达和蛋白质水平。通过实时PCR分析评估基因表达，并通过蛋白质印迹评估大鼠中的蛋白质水平。结果表明，脑室内（icv）注射OrxA可以增加D2R的基因转录和蛋白质含量，但不能修饰D1R。通过在NAc / Shell中输注OrxA也可以确认这种效果。我们的结果首次证明OrxA诱导NAc中D2R基因和蛋白质的上调。