Nociceptin and
nociceptin receptor, which show structural similarities to
opioid peptides and
opioid receptors, respectively, have been recently 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
hyperalgesia and hypolocomotion, whereas the
nociceptin receptor-knockout mice show no significant abnormalities in nociceptive thresholds and locomotion. 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 transfected with the
nociceptin receptor cDNA showed that
NalBzoH competed with [3H]
nociceptin binding and attenuated the
nociceptin-induced inhibition of cAMP accumulation. Furthermore, behavioral studies demonstrated that
NalBzoH completely inhibited
nociceptin-induced
hyperalgesia and hypolocomotion. It is therefore likely that
NalBzoH can act as a potent antagonist for the
nociceptin receptor in vivo. In wild-type mice,
NalBzoH induced antinociception but did not affect locomotor activity. In contrast, in the knockout mice, no significant changes in nociception and locomotion were induced by
NalBzoH. These results clearly suggest that the
nociceptin system takes part in the physiological regulation of nociceptive thresholds but not in the basal modulation of locomotion.