title: Involvement of local orphanin FQ in the tolerance induced by repeated microinjections of morphine into ventrolateral periaqueductal gray in rats.
abstract: The present study evaluated the role of ventrolateral periaqueductal gray (vlPAG)-located orphanin-FQ (OFQ) in the opioid tolerance induced by repeated microinjections of morphine (MOR) into vlPAG. Microinjection of MOR (5 microg/0.5 microl) into vlPAG caused antinociception as quantified with the tail flick and the hot plate tests. When MOR microinjection was repeated twice daily, the antinociceptive effect disappeared within 2 days (tolerance). However, if MOR microinjection was preceded by the OFQ receptor antagonist nocistatin (NST; 1 ng/0.5 microl), the microinjections of MOR did not induce tolerance. If NST microinjections were suspended, subsequent MOR microinjections induced tolerance. In MOR-tolerant rats, a single NST microinjection into vlPAG was enough to restore the antinociceptive effect of MOR. Furthermore, if OFQ (1 ng/0.5 microl) was microinjected into vlPAG, then a MOR microinjection administered 15 min later into vlPAG did not elicit antinociception. Finally, opioid tolerance induced by repeated systemic MOR injections (5 mg/kg, i.p.) was reversed by a single microinjection of NST into vlPAG. This emphasizes the central importance of vlPAG-located OFQ in the MOR tolerance.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of First Clinical College, China Medical University, Shenyang, PR China.
authors.forename: Zhi Jun
authors.initials: ZJ
authors.lastname: Ge
authors.forename: Li Cai
authors.initials: LC
authors.lastname: Zhang
authors.forename: Yin Ming
authors.initials: YM
authors.lastname: Zeng
authors.forename: Ti Jun
authors.initials: TJ
authors.lastname: Dai
authors.forename: Li
authors.initials: L
authors.lastname: Chang
authors.forename: Jun Ke
authors.initials: JK
authors.lastname: Wang
authors.forename: Guo Xin
authors.initials: GX
authors.lastname: Cui
authors.forename: Yong Fei
authors.initials: YF
authors.lastname: Tan
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Zhao
authors.forename: Guo Jun
authors.initials: GJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000494:pharmacology / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D009020:Morphine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C111148:nocistatin; C000722285:Oprl1 protein, rat