کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4342116 | 1295857 | 2006 | 7 صفحه PDF | دانلود رایگان |
Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that stimulates corticosterone release after i.c.v. administration in non-stressed rats. We employed in situ hybridization histochemistry to investigate N/OFQ–stimulated activation of the HPA axis at the hypothalamic and pituitary level. We have demonstrated that N/OFQ–induced activation of the HPA axis is mediated via the central N/OFQ peptide receptor (NOP) using the recently described selective NOP antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-101).We found that, at 30 min post–i.c.v. injection, N/OFQ dose-dependently increased plasma adrenocorticotrophin hormone and corticosterone compared with the vehicle-injected controls. N/OFQ (1.0 μg) significantly increased CRF mRNA but not AVP mRNA within the parvocellular hypothalamic paraventricular nucleus compared with the control group, and significantly increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary. While UFP-101 (1.0 μg) alone had no significant effect on plasma corticosterone concentration it blocked the effect of N/OFQ (1.0 μg) on plasma corticosterone levels when compared with N/OFQ administered alone. UFP-101 also blocked the N/OFQ-induced increase in CRF mRNA and POMC mRNA. These results demonstrate that centrally administered N/OFQ activates the HPA axis via up-regulation of CRF and POMC mRNA and stimulation of corticosterone release in rats. Further, we have demonstrated for the first time that the selective NOP receptor antagonist UFP-101 blocks these effects indicating that N/OFQ–induced HPA axis activation is mediated via central NOP receptors.
Journal: Neuroscience - Volume 141, Issue 4, 2006, Pages 2051–2057