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Updated: Jun 27, 2026
Assessment of Memory Function in Pilocarpine-induced Epileptic Mice
Published on: June 4, 2020
Distinct effects of nociceptin analogs on scopolamine-induced memory impairment in mice
Masaya Miwa1, Chieko Shinki, Shogo Uchida
1Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Nagoya, Japan.
Abstract:
Nociceptin, also known as orphanin FQ, binds to opioid receptor like-1 (NOP) receptors. Nociceptin and NOP receptor play important roles in several physiological functions in the central nervous system. We reported that although high doses of nociceptin impaired learning and memory and these effects were blocked by nocistatin, naloxone benzoylhydrazone and [NPhe(1)]nociceptin(1-13)NH(2), low doses of nociceptin improved scopolamine- or mecamylamine-induced impairment of learning and memory, and these ameliorating effects were not blocked by these antagonists. In the present study, to confirm our previous findings, the effects of [Arg(14), Lys(15)]nociceptin and [(pF)Phe(4)]nociceptin(1-13)NH(2), highly potent and long-lasting nociceptin analogs, on the memory impairment induced by scopolamine using the Y-maze and step-down type passive avoidance tests were investigated. [Arg(14), Lys(15)]Nociceptin (0.1 and/or 1 pmol/mouse, i.c.v.) significantly improved impairment of memory function. Although this analog was about 30 times more potent than nociceptin, the doses ameliorating these memory impairments were comparable to those of the natural ligand nociceptin. The ameliorating effects of [Arg(14), Lys(15)]nociceptin were not blocked by an NOP receptor antagonist, [NPhe(1)]nociceptin(1-13)NH(2). Interestingly, another potent nociceptin analog, [(pF)Phe(4)]nociceptin(1-13)NH(2) could not improve impairment of memory function. These results confirmed that there are novel mechanisms underlying these ameliorating effects and these seem not to be mediated via an NOP receptor.
Insights
Low doses of nociceptin analogs, [Arg(14), Lys(15)]nociceptin, improve memory impairment via novel mechanisms. These effects were not blocked by NOP receptor antagonists, suggesting a non-NOP receptor pathway for memory enhancement.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Nociceptin, also known as orphanin FQ, interacts with opioid receptor like-1 (NOP) receptors.
- Nociceptin and NOP receptors are implicated in central nervous system physiological functions, including learning and memory.
- Previous research indicated low-dose nociceptin improved memory impairment, with effects not blocked by certain antagonists.
Purpose of the Study:
- To confirm previous findings on nociceptin's effects on memory.
- To investigate the effects of potent nociceptin analogs, [Arg(14), Lys(15)]nociceptin and [(pF)Phe(4)]nociceptin(1-13)NH(2), on scopolamine-induced memory impairment.
Main Methods:
- Utilized Y-maze and step-down type passive avoidance tests to assess memory function.
- Administered [Arg(14), Lys(15)]nociceptin and [(pF)Phe(4)]nociceptin(1-13)NH(2) intracerebroventricularly (i.c.v.) in mice.
- Investigated the role of NOP receptors by using the antagonist [NPhe(1)]nociceptin(1-13)NH(2).
Main Results:
- [Arg(14), Lys(15)]nociceptin (0.1 and/or 1 pmol/mouse, i.c.v.) significantly improved memory impairment.
- The memory-ameliorating effects of [Arg(14), Lys(15)]nociceptin were not blocked by the NOP receptor antagonist [NPhe(1)]nociceptin(1-13)NH(2).
- The potent analog [(pF)Phe(4)]nociceptin(1-13)NH(2) did not improve memory impairment.
Conclusions:
- Novel mechanisms, potentially independent of NOP receptors, underlie the memory-enhancing effects of certain nociceptin analogs.
- [Arg(14), Lys(15)]nociceptin demonstrates significant memory improvement capabilities.
- Further research is warranted to elucidate the precise pathways involved in these non-NOP receptor-mediated effects.
