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 orph anin FQ (OFQ) blocks opioid-induced antinociception in a variety of animal models of pain. In the present study, we sought to investigate the inhibito ry effect of OFQ on morphine-induced antinociception using the hot plate te st in rats and to examine whether tolerance develops to the anti-opioid eff ect of the peptide. Microinjection of OFQ (50 nmol, i.c.v.) significantly a ttenuated the antinociceptive effect of morphine without affecting baseline hot plate latencies, suggesting that modification of morphine-induced anti nociception can be achieved via activation of the ORL-1 receptor by OFQ wit h no apparent mu opioid receptor blockade or interference with basal nocice ptive responses. Chronic treatment with OFQ (50 nmol/day for 5 days) produc ed 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. (C) 1999 Lippincott Wil liams & Wilkins.