Neuronal mechanism of nociceptin-induced modulation of learning and memory

Involvement of N-methyl-D-aspartate receptors

T. Mamiya, K. Yamada, Y. Miyamoto, N. König, Y. Watanabe, Y. Noda, Toshitaka Nabeshima

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Nociceptin (also called orphanin FQ) is an endogenous heptadecapeptide that activates the opioid receptor-like 1 (ORL 1 ) receptor. Nociceptin system not only affects the nociception and locomotor activity, but also regulates learning and memory in rodents. We have previously reported that long-term potentiation and memory of ORL 1 receptor knockout mice are enhanced compared with those in wild-type mice. Here, we show the neuronal mechanism of nociceptin-induced modulation of learning and memory. Retention of fear-conditioned contextual memory was significantly enhanced in the ORL 1 receptor knockout mice without any changes in cued conditioned freezing. Inversely, in the wild-type mice retention of contextual, but not cued, conditioning freezing behavior was suppressed by exogenous nociceptin when it was administered into the cerebroventricle immediately after the training. ORL 1 receptor knockout mice exhibited a hyperfunction of N-methyl-D-aspartate (NMDA) receptor, as evidenced by an increase in [ 3 H]MK-801 binding, NMDA-evoked 45 Ca 2+ uptake and activation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activity and its phosphorylation as compared with those in wild-type mice. The NMDA-induced CaMKII activation in the hippocampal slices of wild-type mice was significantly inhibited by exogenous nociceptin via a pertussis toxin-sensitive pathway. However, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor GluR1 subunit at Ser 831 and Ser 845 , and NMDA receptor subunit NR2B at Thr 286 were phosphorylated similarly after NMDA receptor stimulation in both type of mice. The expressions of GluR1 and GluR2 also did not change, but the levels of polysialylated form of neuronal cell adhesion molecule (N-CAM) were reduced in the ORL 1 receptor knockout as compared with wild-type mice. These results suggest that nociceptin system negatively modulates learning and memory through the regulation of NMDA receptor function and the expression of N-CAM.

Original languageEnglish
Pages (from-to)752-765
Number of pages14
JournalMolecular Psychiatry
Volume8
Issue number8
DOIs
Publication statusPublished - 21-08-2003
Externally publishedYes

Fingerprint

N-Methyl-D-Aspartate Receptors
Learning
Opioid Receptors
Neuronal Cell Adhesion Molecules
Knockout Mice
Calcium-Calmodulin-Dependent Protein Kinase Type 2
N-Methylaspartate
Freezing
Isoxazoles
Calcium-Calmodulin-Dependent Protein Kinases
Nociception
Dizocilpine Maleate
Long-Term Memory
Long-Term Potentiation
Pertussis Toxin
Locomotion
nociceptin
Fear
Rodentia
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Mamiya, T. ; Yamada, K. ; Miyamoto, Y. ; König, N. ; Watanabe, Y. ; Noda, Y. ; Nabeshima, Toshitaka. / Neuronal mechanism of nociceptin-induced modulation of learning and memory : Involvement of N-methyl-D-aspartate receptors. In: Molecular Psychiatry. 2003 ; Vol. 8, No. 8. pp. 752-765.
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Neuronal mechanism of nociceptin-induced modulation of learning and memory : Involvement of N-methyl-D-aspartate receptors. / Mamiya, T.; Yamada, K.; Miyamoto, Y.; König, N.; Watanabe, Y.; Noda, Y.; Nabeshima, Toshitaka.

In: Molecular Psychiatry, Vol. 8, No. 8, 21.08.2003, p. 752-765.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neuronal mechanism of nociceptin-induced modulation of learning and memory

T2 - Involvement of N-methyl-D-aspartate receptors

AU - Mamiya, T.

AU - Yamada, K.

AU - Miyamoto, Y.

AU - König, N.

AU - Watanabe, Y.

AU - Noda, Y.

AU - Nabeshima, Toshitaka

PY - 2003/8/21

Y1 - 2003/8/21

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