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.