LOSS OF ANTINOCICEPTION INDUCED BY NALOXONE BENZOYLHYDRAZONE IN NOCICEPTIN RECEPTOR-KNOCKOUT MICE

Nociceptin and nociceptin receptor, which show structural similarities to opioid peptides and opioid receptors, respectively, have been rece ntly found to constitute a novel neuromodulatory system. In the brain, however, the physiological role of the modulation via the nociceptin receptor is still unclear. Administered nociceptin produces hyperalges ia and hypolocomotion, whereas the nociceptin receptor-knockout mice s how no significant abnormalities in nociceptive thresholds and locomot ion. To clarify possible involvement of the nociceptin receptor in the regulation of nociception and locomotion, we made use of the knockout mice and naloxone benzoylhydrazone (NalBzoH) identified originally as a ligand for opioid receptors, Experiments on the cultured cells tran sfected with the nociceptin receptor cDNA showed that NalBzoH competed with [H-3]nociceptin binding and attenuated the nociceptin-induced in hibition of cAMP accumulation. Furthermore, behavioral studies demonst rated that NalBzoH completely inhibited nociceptin-induced hyperalgesi a and hypolocomotion. It is therefore likely that NalBzoH can act as a potent antagonist for the nociceptin receptor in vivo. In wild-type m ice, NalBzoH induced antinociception but did not affect locomotor acti vity. In contrast, in the knockout mice, no significant changes in noc iception and locomotion were induced by NalBzoH. These results clearly suggest that the nociceptin system takes part in the physiological re gulation of nociceptive thresholds but not in the basal modulation of locomotion.