Tolerance develops to the inhibitory effect of orphanin FQ on morphine-induced antinociception in the rat.
Recent studies that intracerebroventricular (i.c.v.) administration of orphanin FQ (OFQ) blocks opioid-induced antinociception in a variety of animal models of pain. In the present study, we sought to investigate the inhibitory effect of OFQ on morphine-induced antinociception using the hot plate test in rats and to examine whether tolerance develops to the anti-opioid effect of the peptide. Microinjection of OFQ (50nmol, i.c.v.) significantly attenuated the antinociceptive effect of morphine without affecting baseline hot plate latencies, suggesting that modification of morphine-induced antinociception can be achieved via activation of the ORL-1 receptor by OFQ with no apparent mu opioid receptor blockade or interference with basal nociceptive responses. Chronic treatment with OFQ (50 nmol/day for 5 days) produced a complete loss of the inhibitory effect of the peptide indicating that tolerance developed to the anti-opioid effect of OFQ. Taken together, these results indicate that neuronal plasticity may occur following chronic use of OFQ as is evident for the other opioid agonists.
Lutfy
K
K
Department of Psychiatry and Biobehavioral Sciences, UCLA, Neuropsychiatric Institute, Los Angeles, CA 90024, USA.
Sharza
S A
SA
Maidment
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NT
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D004361:Drug Tolerance; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors*; D009473:Neuronal Plasticity / Q000187:drug effects; D018847:Opioid Peptides / Q000494:pharmacology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D000701:Analgesics, Opioid; D009020:Morphine; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin