Abstract
Nociceptin binds to nociceptin opioid peptide (NOP) receptors. We reported that although high doses of nociceptin impaired memory function and that these effects were mediated via NOP receptors, low doses of nociceptin attenuated the memory impairment, and these attenuating effects were not mediated via NOP receptors. Even very low doses of nociceptin were biologically active and suggested a certain binding site for this peptide, but the mechanism underlying this attenuating effect has not yet been elucidated. In the present study, we investigated the effect of an intrahippocampal injection (i.h.) of nociceptin on memory impairment induced by U0126, a MEK inhibitor, and Rp-cAMPS, a PKA inhibitor in a step-down type passive avoidance test. U0126 (2.63. nmol/mouse, i.h.) impaired memory formation and training-dependent phosphorylation of ERK2 in the hippocampus. Co-administration of nociceptin (10. fmol/mouse) significantly attenuated memory impairment, while it did not attenuate the inhibition of training-dependent phosphorylation of ERK2 induced by U0126. On the other hand, nociceptin did not attenuate memory impairment induced by Rp-cAMPS (0.448. nmol/mouse, i.h.). Nociceptin (1. fmol/mouse) also attenuated U0126 (5.26. nmol/mouse)-induced memory impairment in NOP receptor knockout mice. Nociceptin was reported to metabolize into fragments (1-13) and (14-17) in vivo, which showed pharmacological activities without affecting NOP receptors. Our findings showed that nociceptin (14-17) (1. fmol/mouse) also attenuated U0126-induced memory impairment, while nociceptin (1-13) (0.1-10. fmol/mouse) did not attenuate memory impairment. These results suggest a novel action site or mechanism for the attenuating effects of nociceptin and its metabolite, and the sequence of nociceptin (14-17) is a critical structure.
| Original language | English |
|---|---|
| Pages (from-to) | 396-405 |
| Number of pages | 10 |
| Journal | Neurobiology of Learning and Memory |
| Volume | 93 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-03-2010 |
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All Science Journal Classification (ASJC) codes
- Experimental and Cognitive Psychology
- Cognitive Neuroscience
- Behavioral Neuroscience
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Nociceptin and its metabolite attenuate U0126-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism. / Miwa, Masaya; Uchida, Shogo; Horiba, Fumika; Takeshima, Hiroshi; Nabeshima, Toshitaka; Hiramatsu, Masayuki.
In: Neurobiology of Learning and Memory, Vol. 93, No. 3, 01.03.2010, p. 396-405.Research output: Contribution to journal › Article
TY - JOUR
T1 - Nociceptin and its metabolite attenuate U0126-induced memory impairment through a nociceptin opioid peptide (NOP) receptor-independent mechanism
AU - Miwa, Masaya
AU - Uchida, Shogo
AU - Horiba, Fumika
AU - Takeshima, Hiroshi
AU - Nabeshima, Toshitaka
AU - Hiramatsu, Masayuki
PY - 2010/3/1
Y1 - 2010/3/1
N2 - Nociceptin binds to nociceptin opioid peptide (NOP) receptors. We reported that although high doses of nociceptin impaired memory function and that these effects were mediated via NOP receptors, low doses of nociceptin attenuated the memory impairment, and these attenuating effects were not mediated via NOP receptors. Even very low doses of nociceptin were biologically active and suggested a certain binding site for this peptide, but the mechanism underlying this attenuating effect has not yet been elucidated. In the present study, we investigated the effect of an intrahippocampal injection (i.h.) of nociceptin on memory impairment induced by U0126, a MEK inhibitor, and Rp-cAMPS, a PKA inhibitor in a step-down type passive avoidance test. U0126 (2.63. nmol/mouse, i.h.) impaired memory formation and training-dependent phosphorylation of ERK2 in the hippocampus. Co-administration of nociceptin (10. fmol/mouse) significantly attenuated memory impairment, while it did not attenuate the inhibition of training-dependent phosphorylation of ERK2 induced by U0126. On the other hand, nociceptin did not attenuate memory impairment induced by Rp-cAMPS (0.448. nmol/mouse, i.h.). Nociceptin (1. fmol/mouse) also attenuated U0126 (5.26. nmol/mouse)-induced memory impairment in NOP receptor knockout mice. Nociceptin was reported to metabolize into fragments (1-13) and (14-17) in vivo, which showed pharmacological activities without affecting NOP receptors. Our findings showed that nociceptin (14-17) (1. fmol/mouse) also attenuated U0126-induced memory impairment, while nociceptin (1-13) (0.1-10. fmol/mouse) did not attenuate memory impairment. These results suggest a novel action site or mechanism for the attenuating effects of nociceptin and its metabolite, and the sequence of nociceptin (14-17) is a critical structure.
AB - Nociceptin binds to nociceptin opioid peptide (NOP) receptors. We reported that although high doses of nociceptin impaired memory function and that these effects were mediated via NOP receptors, low doses of nociceptin attenuated the memory impairment, and these attenuating effects were not mediated via NOP receptors. Even very low doses of nociceptin were biologically active and suggested a certain binding site for this peptide, but the mechanism underlying this attenuating effect has not yet been elucidated. In the present study, we investigated the effect of an intrahippocampal injection (i.h.) of nociceptin on memory impairment induced by U0126, a MEK inhibitor, and Rp-cAMPS, a PKA inhibitor in a step-down type passive avoidance test. U0126 (2.63. nmol/mouse, i.h.) impaired memory formation and training-dependent phosphorylation of ERK2 in the hippocampus. Co-administration of nociceptin (10. fmol/mouse) significantly attenuated memory impairment, while it did not attenuate the inhibition of training-dependent phosphorylation of ERK2 induced by U0126. On the other hand, nociceptin did not attenuate memory impairment induced by Rp-cAMPS (0.448. nmol/mouse, i.h.). Nociceptin (1. fmol/mouse) also attenuated U0126 (5.26. nmol/mouse)-induced memory impairment in NOP receptor knockout mice. Nociceptin was reported to metabolize into fragments (1-13) and (14-17) in vivo, which showed pharmacological activities without affecting NOP receptors. Our findings showed that nociceptin (14-17) (1. fmol/mouse) also attenuated U0126-induced memory impairment, while nociceptin (1-13) (0.1-10. fmol/mouse) did not attenuate memory impairment. These results suggest a novel action site or mechanism for the attenuating effects of nociceptin and its metabolite, and the sequence of nociceptin (14-17) is a critical structure.
UR - http://www.scopus.com/inward/record.url?scp=77950689980&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77950689980&partnerID=8YFLogxK
U2 - 10.1016/j.nlm.2009.12.006
DO - 10.1016/j.nlm.2009.12.006
M3 - Article
C2 - 20026233
AN - SCOPUS:77950689980
VL - 93
SP - 396
EP - 405
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
SN - 1074-7427
IS - 3
ER -