Rodi Donata, Polidori Carlo, Bregola Gianni, Zucchini Silvia, Simonato Michele, Massi Maurizio
Department of Clinical and Experimental Medicine, Section of Pharmacology, and Neuroscience Center, University of Ferrara, Ferrara, Italy.
Brain Res. 2002 Dec 13;957(2):354-61. doi: 10.1016/s0006-8993(02)03678-8.
Forebrain injections of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP opioid receptor, previously referred to as ORL1 or OP4 receptor, stimulate feeding in freely feeding rats, while the NOP receptor antagonist [Nphe(1)]N/OFQ(1-13)NH(2) inhibits food deprivation-induced feeding. To further evaluate whether the N/OFQ-NOP receptor system plays a physiological role in feeding control, the present study evaluated forebrain mRNA levels for the N/OFQ precursor (pro-N/OFQ), as well as for the NOP receptor in food deprived rats. The results obtained show that food deprived rats have lower mRNA levels for the NOP receptor in several forebrain regions; a significant reduction was found in the paraventricular and lateral hypothalamic nuclei and in the central nucleus of the amygdala. Food deprived rats also exhibited lower pro-N/OFQ mRNA levels in the central amygdala. These results suggest that the N/OFQ-NOP receptor system may have a physiological role in feeding control. The observation that food deprivation reduces gene expression of the N/OFQ-NOP receptor system is apparently not consistent with a direct hyperphagic action for N/OFQ. Taking into account that N/OFQ exerts inhibitory actions at cellular level, the present results may be in keeping with the hypothesis that N/OFQ stimulates feeding by inhibiting neurons inhibitory for food intake; under conditions of food deprivation, these neurons may be silent and the N/OFQ-NOP receptor system, which controls them, may also be regulated at a lower level. Consistently, in the present study N/OFQ stimulated food intake in freely feeding rats, but did not further increase feeding in food deprived rats.
向大鼠前脑注射痛敏肽/孤啡肽FQ（N/OFQ），即NOP阿片受体的内源性配体，该受体先前被称为ORL1或OP4受体，可刺激自由进食大鼠的进食行为，而NOP受体拮抗剂[Nphe(1)]N/OFQ(1-13)NH(2)可抑制食物剥夺诱导的进食。为了进一步评估N/OFQ-NOP受体系统在进食控制中是否发挥生理作用，本研究评估了食物剥夺大鼠前脑中N/OFQ前体（前N/OFQ）以及NOP受体的mRNA水平。结果表明，食物剥夺大鼠前脑几个区域的NOP受体mRNA水平较低；在室旁核、下丘脑外侧核和杏仁核中央核中发现显著降低。食物剥夺大鼠杏仁核中央的前N/OFQ mRNA水平也较低。这些结果表明，N/OFQ-NOP受体系统可能在进食控制中发挥生理作用。食物剥夺降低N/OFQ-NOP受体系统基因表达这一观察结果显然与N/OFQ直接的促食作用不一致。考虑到N/OFQ在细胞水平发挥抑制作用，目前的结果可能与以下假设一致，即N/OFQ通过抑制对食物摄入有抑制作用的神经元来刺激进食；在食物剥夺的情况下，这些神经元可能处于沉默状态，而控制它们的N/OFQ-NOP受体系统也可能在较低水平受到调节。同样，在本研究中，N/OFQ刺激自由进食大鼠的食物摄入量，但并未进一步增加食物剥夺大鼠的进食量。
