Y. Noda et al., LOSS OF ANTINOCICEPTION INDUCED BY NALOXONE BENZOYLHYDRAZONE IN NOCICEPTIN RECEPTOR-KNOCKOUT MICE, The Journal of biological chemistry, 273(29), 1998, pp. 18047-18051
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.