Effect of nociceptin and [Phe(1)Psi (CH2-NH) Gly(2)]-nociceptin-(1-13)-NH2on tonic activity of rat hypothalamic neurons

The effect of nociceptin, an endogenous ligand for a unique member of the c loned opioid receptor family ORL1-receptor, on tonic activity of neurons in the preoptic area/anterior hypothalamus (PO/AH) has been examined in rat b rain slices using extracellular recordings. Nociceptin (1, 10 and 100 nM) d ecreased dose-dependently tonic activity of PO/AH neurons. This effect was not significantly different from the effect of [Phe(1)Psi (CH2-NH) Gly(2)]- nociceptin-(1-13)-NH2 (1, 10 and 100 nM), recently proposed as a selective antagonist of the nociceptin receptor. Thus, [Phe(1)Psi (CH2-NH) Gly(2)]noc iceptin-(1-13)-NH2 appears to be an agonist rather than an antagonist of no ciceptin (ORL1) receptor in rat PO/AH neurons. However, there was neither a ntagonism nor additive synergism when nociceptin, and [Phe(1)Psi (CH2-NH) G ly(2)]-nociceptin-(1-13 )-NH2 were applied simultaneously at equimolar conc entrations. The effect of nociceptin on tonic activity of rat PO/AH neurons was not blocked by selective mu-, kappa- and delta-opioid receptor antagon ists (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nor-binaltorphimine a nd naltrindol, respectively) at 10 times higher concentrations than nocicep tin. These data suggest that the effect of nociceptin on tonic activity of PO/AH neurons is not due to an action on mu- kappa-, or delta-opioid recept ors but results from a specific effect on the ORL1-receptor. (C) 1999 Elsev ier Science ireland Ltd. All rights reserved.