Behavioral pharmacological characterization of mice lacking the nociceptin receptor

Y. Noda, T. Mamiya, Toshitaka Nabeshima

Research output: Contribution to journalShort survey

3 Citations (Scopus)

Abstract

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 central nervous system, however, the physiological role of modulation via the nociceptin receptor is still unclear. Here, we report the behavioral pharmacological characterization of mice lacking the nociceptin receptor. Nociceptin produced hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice showed no significant abnormalities in nociceptive thresholds (tail- flick, hot-plate, electric, and acetic acid-induced writhing tests) and locomotion. In the learning and memory tests, nociceptin induced impairment of learning and memory in wild-type mice. Nociceptin receptor-knockout mice possessed greater learning ability and had better memory than wild-type mice. These results suggest that the nociceptin system plays a role in regulation of nociception or locomotion and seems to play negative roles in learning and memory. Next, we compared nociceptive responses induced by various opioids between the nociceptin receptor-knockout and wild-type mice. As previously reported, morphine (μ-opioid receptor agonist), U-50,488H (K1-opioid receptor agonist), and naloxone benzoylhydrazone (NalBzoH; K3-opioid receptor agonist) induced antinociceptive effects in wild-type mice. Surprisingly, knockout mice lacked the antinociceptive effect induced by NalBzoH, but not by morphine and U-50,488H. Further, NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion in wild-type mice. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed in [3H]-nociceptin binding and attenuated the nociceptin-induced inhibition of cyclic AMP accumulation induced by forskolin. These results clearly suggest that NalBzoH acts as a potent antagonist for the nociceptin receptor. Our studies suggest that the nociceptive system and/or learning and memory processes could be modulated by ligands to the nociceptin receptor, and further that the antagonists are worth testing for the alleviation of pain and memory disorders.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalJapanese Journal of Psychopharmacology
Volume19
Issue number2
Publication statusPublished - 01-01-1999

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Pharmacology
Opioid Receptors
Knockout Mice
Learning
(trans)-Isomer 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide
Hyperalgesia
Locomotion
nociceptin receptor
Somatoform Disorders
Aptitude
Nociception
Peptide Receptors
Opioid Peptides
mu Opioid Receptor
Memory Disorders
Colforsin
nociceptin
Acetic Acid
Cyclic AMP
Morphine

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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title = "Behavioral pharmacological characterization of mice lacking the nociceptin receptor",
abstract = "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 central nervous system, however, the physiological role of modulation via the nociceptin receptor is still unclear. Here, we report the behavioral pharmacological characterization of mice lacking the nociceptin receptor. Nociceptin produced hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice showed no significant abnormalities in nociceptive thresholds (tail- flick, hot-plate, electric, and acetic acid-induced writhing tests) and locomotion. In the learning and memory tests, nociceptin induced impairment of learning and memory in wild-type mice. Nociceptin receptor-knockout mice possessed greater learning ability and had better memory than wild-type mice. These results suggest that the nociceptin system plays a role in regulation of nociception or locomotion and seems to play negative roles in learning and memory. Next, we compared nociceptive responses induced by various opioids between the nociceptin receptor-knockout and wild-type mice. As previously reported, morphine (μ-opioid receptor agonist), U-50,488H (K1-opioid receptor agonist), and naloxone benzoylhydrazone (NalBzoH; K3-opioid receptor agonist) induced antinociceptive effects in wild-type mice. Surprisingly, knockout mice lacked the antinociceptive effect induced by NalBzoH, but not by morphine and U-50,488H. Further, NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion in wild-type mice. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed in [3H]-nociceptin binding and attenuated the nociceptin-induced inhibition of cyclic AMP accumulation induced by forskolin. These results clearly suggest that NalBzoH acts as a potent antagonist for the nociceptin receptor. Our studies suggest that the nociceptive system and/or learning and memory processes could be modulated by ligands to the nociceptin receptor, and further that the antagonists are worth testing for the alleviation of pain and memory disorders.",
author = "Y. Noda and T. Mamiya and Toshitaka Nabeshima",
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Behavioral pharmacological characterization of mice lacking the nociceptin receptor. / Noda, Y.; Mamiya, T.; Nabeshima, Toshitaka.

In: Japanese Journal of Psychopharmacology, Vol. 19, No. 2, 01.01.1999, p. 73-78.

Research output: Contribution to journalShort survey

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T1 - Behavioral pharmacological characterization of mice lacking the nociceptin receptor

AU - Noda, Y.

AU - Mamiya, T.

AU - Nabeshima, Toshitaka

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N2 - 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 central nervous system, however, the physiological role of modulation via the nociceptin receptor is still unclear. Here, we report the behavioral pharmacological characterization of mice lacking the nociceptin receptor. Nociceptin produced hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice showed no significant abnormalities in nociceptive thresholds (tail- flick, hot-plate, electric, and acetic acid-induced writhing tests) and locomotion. In the learning and memory tests, nociceptin induced impairment of learning and memory in wild-type mice. Nociceptin receptor-knockout mice possessed greater learning ability and had better memory than wild-type mice. These results suggest that the nociceptin system plays a role in regulation of nociception or locomotion and seems to play negative roles in learning and memory. Next, we compared nociceptive responses induced by various opioids between the nociceptin receptor-knockout and wild-type mice. As previously reported, morphine (μ-opioid receptor agonist), U-50,488H (K1-opioid receptor agonist), and naloxone benzoylhydrazone (NalBzoH; K3-opioid receptor agonist) induced antinociceptive effects in wild-type mice. Surprisingly, knockout mice lacked the antinociceptive effect induced by NalBzoH, but not by morphine and U-50,488H. Further, NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion in wild-type mice. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed in [3H]-nociceptin binding and attenuated the nociceptin-induced inhibition of cyclic AMP accumulation induced by forskolin. These results clearly suggest that NalBzoH acts as a potent antagonist for the nociceptin receptor. Our studies suggest that the nociceptive system and/or learning and memory processes could be modulated by ligands to the nociceptin receptor, and further that the antagonists are worth testing for the alleviation of pain and memory disorders.

AB - 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 central nervous system, however, the physiological role of modulation via the nociceptin receptor is still unclear. Here, we report the behavioral pharmacological characterization of mice lacking the nociceptin receptor. Nociceptin produced hyperalgesia and hypolocomotion, whereas the nociceptin receptor-knockout mice showed no significant abnormalities in nociceptive thresholds (tail- flick, hot-plate, electric, and acetic acid-induced writhing tests) and locomotion. In the learning and memory tests, nociceptin induced impairment of learning and memory in wild-type mice. Nociceptin receptor-knockout mice possessed greater learning ability and had better memory than wild-type mice. These results suggest that the nociceptin system plays a role in regulation of nociception or locomotion and seems to play negative roles in learning and memory. Next, we compared nociceptive responses induced by various opioids between the nociceptin receptor-knockout and wild-type mice. As previously reported, morphine (μ-opioid receptor agonist), U-50,488H (K1-opioid receptor agonist), and naloxone benzoylhydrazone (NalBzoH; K3-opioid receptor agonist) induced antinociceptive effects in wild-type mice. Surprisingly, knockout mice lacked the antinociceptive effect induced by NalBzoH, but not by morphine and U-50,488H. Further, NalBzoH completely inhibited nociceptin-induced hyperalgesia and hypolocomotion in wild-type mice. Experiments on the cultured cells transfected with the nociceptin receptor cDNA showed that NalBzoH competed in [3H]-nociceptin binding and attenuated the nociceptin-induced inhibition of cyclic AMP accumulation induced by forskolin. These results clearly suggest that NalBzoH acts as a potent antagonist for the nociceptin receptor. Our studies suggest that the nociceptive system and/or learning and memory processes could be modulated by ligands to the nociceptin receptor, and further that the antagonists are worth testing for the alleviation of pain and memory disorders.

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