Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Behav Brain Res. 2010 Jan 20;206(2):313-7. doi: 10.1016/j.bbr.2009.09.017. Epub 2009 Sep 16.
Agonists of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor stimulate food intake. Concordantly, neuroanatomical localization of NOP receptor mRNA has revealed it to be highly expressed in brain regions associated with the regulation of energy balance. However, the specific mechanisms and neurochemical pathways through which physiological N/OFQ influences appetite are not well understood. To investigate this, we examined nutritional state-associated changes in NOP receptor mRNA levels throughout the rostrocaudal extent of the rat brain using in situ hybridization histochemistry (ISHH) and quantitative densitometry analysis. We observed a significant downregulation of NOP receptor mRNA in the dorsal raphe nucleus (DRN) of fasted rats compared to free-feeding rats. In contrast, no difference in NOP receptor mRNA expression was observed in the supraoptic, parventricular, ventromedial, arcuate or dorsomedial nuclei of the hypothalamus, the red nucleus, the locus coeruleus or the hypoglossal nucleus in the fasted or fed state. These data suggest that the endogenous N/OFQ system is responsive to changes in energy balance and that NOP receptors specifically within the DRN may be physiologically relevant to N/OFQ's effects on appetite.
孤啡肽（N/OFQ）肽（NOP）受体激动剂刺激食物摄入。相应地，NOP 受体 mRNA 的神经解剖学定位表明，它在与能量平衡调节相关的大脑区域中高度表达。然而，生理 N/OFQ 影响食欲的具体机制和神经化学途径尚不清楚。为了研究这一点，我们使用原位杂交组织化学（ISHH）和定量密度测量分析，检查了整个大鼠脑的 NOP 受体 mRNA 水平与营养状态相关的变化。与自由喂养的大鼠相比，我们观察到禁食大鼠中背侧中缝核（DRN）中的 NOP 受体 mRNA 明显下调。相比之下，在下丘脑的视上核、室旁核、腹内侧核、弓状核或背内侧核、红核、蓝斑核或舌下核中，禁食或进食状态下的 NOP 受体 mRNA 表达没有差异。这些数据表明，内源性 N/OFQ 系统对能量平衡的变化有反应，并且 DRN 中的 NOP 受体可能与 N/OFQ 对食欲的影响在生理上相关。
