The functional antiopioid action of the ventrolateral periaqueductal gray nociceptin/orphanin FQ and nociceptin receptor system underlies DAMGO analgesic tolerance.
Nociceptin/Orphanin FQ (N/OFQ) counteracts supraspinal opioid effects and plays a role in antinociceptive morphine tolerance. Therefore, in the present study, the selective mu-opioid agonist [D-Ala(2)-NMe-Phe(4)-Gly-ol(5)]-enkephalin (DAMGO) was used. Repeated injection of DAMGO (1 microg/ 1 microl) into the ventrolateral periaqueductal gray (vlPAG), a key site for the development of opioid tolerance, induced analgesia that lasted up to 3 days. In DAMGO-tolerant rats, injection of the N/OFQ antagonist (+/-)-J 113397 (4 microg/1 microl), into the same site, restored the antinociceptive effect of DAMGO. If (+/-)-J 113397 treatment preceded each DAMGO injection, tolerance did not develop. Inhibition of N/OFQ signaling can reverse and prevent the development of DAMGO tolerance in the vlPAG. The results confirm that N/OFQ acts as a functional opioid antagonist.
Parenti
Carmela
C
Department of Pharmaceutical Sciences - Pharmacology Section, University of Catania, Italy. cparenti @ unict.it
Scoto
Giovanna M
GM
D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D004361:Drug Tolerance; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000378:metabolism; D010146:Pain; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D001562:Benzimidazoles; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010880:Piperidines; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C402921:J 113397; C000722285:Oprl1 protein, rat