1. The functional antiopioid action of the ventrolateral periaqueductal gray nociceptin/orphanin FQ and nociceptin receptor system underlies DAMGO analgesic tolerance.
- Author
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Parenti C and Scoto GM
- Subjects
- Analgesia, Animals, Benzimidazoles pharmacology, Drug Tolerance, Enkephalin, Ala(2)-MePhe(4)-Gly(5)- administration & dosage, Male, Morphine pharmacology, Opioid Peptides metabolism, Pain, Periaqueductal Gray drug effects, Piperidines pharmacology, Rats, Rats, Sprague-Dawley, Vasodilator Agents administration & dosage, Vasodilator Agents metabolism, Nociceptin Receptor, Nociceptin, Analgesics, Opioid pharmacology, Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology, Narcotic Antagonists pharmacology, Periaqueductal Gray physiology, Receptors, Opioid metabolism
- Abstract
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., (2010 S. Karger AG, Basel.)
- Published
- 2010
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