Involvement of ORL1 receptor and ERK kinase in the orphanin FQ-induced nociception in the nucleus accumbens of rats.
Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide, which has been identified as an endogenous ligand of the opioid receptor-like (ORL1) receptor. The present study investigated the nociceptive effect of intra-nucleus accumbens (intra-NAc) injection of OFQ, and the involvement of ERK pathway in such effect. Intra-NAc injection of OFQ (0.1, 0.5, 1 nmol) dose-dependently decreased the nociceptive thresholds on the hindpaw withdrawal response to thermal and mechanical stimulation in rats. Moreover, the intra-NAc injection of OFQ-induced decreases in HWLs were antagonized by intra-NAc injection of (Nphe(1))nociceptin(1-13)NH(2), an antagonist of ORL1 receptor, in a dose-dependent way. Furthermore, the OFQ-induced nociception could be attenuated by pretreatment with the mitogen-activated protein kinase/ERK kinase (MEK) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(2-aminopheylthio)butadiene (U0126). Our results demonstrate that OFQ induces nociceptive effects in NAc. The effect was blocked by the antagonist (Nphe(1))nociceptin(1-13)NH(2) and attenuated by U0126, suggesting that the activation of ERK pathways is involved in the OFQ-induced nociceptive effect in the NAc of rats.
Chen
Li-Ying
LY
Neurobiology Laboratory and National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences Peking University, Beijing 100871, PR China.
Huang
Jia-Xin
JX
Yu
Long-Chuan
LC
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology*; D018847:Opioid Peptides / Q000008:administration & dosage* / Q000494:pharmacology; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002070:Butadienes; D009570:Nitriles; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C113580:U 0126; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C000722285:Oprl1 protein, rat