Involvement of local orphanin FQ in the tolerance induced by repeated microinjections of morphine into ventrolateral periaqueductal gray in rats.
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.
Ge
Zhi Jun
ZJ
Department of Anesthesiology, Affiliated Hospital of First Clinical College, China Medical University, Shenyang, PR China.
Zhang
Li Cai
LC
Zeng
Yin Ming
YM
Dai
Ti Jun
TJ
Chang
Li
L
Wang
Jun Ke
JK
Cui
Guo Xin
GX
Tan
Yong Fei
YF
Zhao
Yan Ping
YP
Liu
Guo Jun
GJ
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
D009020:Morphine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C111148:nocistatin; C000722285:Oprl1 protein, rat