NeuropharmacologyTolerance develops to the inhibitory effect of orphanin FQ on morphine-induced antinociception in the ratLutfy, Kabuirullah1,2; Sharza, Shawn A.1; Maidment, Nigel T.1 Author Information 1Department of Psychiatry and Biobehavioral Sciences, UCLA, Neuropsychiatric Institute, 760 Westwood Plaza, Los Angeles, CA 90024, USA 2Corresponding Author: Kabuirullah Lutfy ACKNOWLEDGEMENTS: We would like to express our gratitude to Drs Niall Murphy and Ghislaine Monteillet-Agius for their critical review of the manuscript, Dr Eckard Weber for the use of hot plate apparatus and Jeff Fein for the synthesis of OFQ. K.L. was supported in part by a NIDA research training grant (T32DA07272) at the UCLA Drug Abuse Research Center. Received 16 September 1998; accepted 4 November 1998 NeuroReport: January 18, 1999 - Volume 10 - Issue 1 - p 103-106 Buy Abstract RECENT studies that intracerebroventricular (i.c.v.) administration of orphanin FQ (OFQ) blocks opioidinduced 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 (50 nmol, 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. © 1999 Lippincott Williams & Wilkins, Inc.