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Research ArticleNEUROPHARMACOLOGY

Persistent Effects of Delayed Treatment with Nefiracetam on the Water Maze Task in Rats with Sustained Cerebral Ischemia

Satoshi Takeo, Tomoko Fukatsu, Keiko Miyake-Takagi, Norio Takagi, Makiko Niimura, Akira Nagakura, Tsuyoshi Ando and Kouichi Tanonaka
Journal of Pharmacology and Experimental Therapeutics February 2003, 304 (2) 513-523; DOI: https://doi.org/10.1124/jpet.102.043653
Satoshi Takeo
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Tomoko Fukatsu
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Keiko Miyake-Takagi
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Norio Takagi
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Makiko Niimura
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Akira Nagakura
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Tsuyoshi Ando
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Kouichi Tanonaka
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Abstract

The present study was aimed at determining whether nefiracetam might have a persistent cognition-enhancing effect in animals with sustained cerebral ischemia. Sustained cerebral ischemia was induced by injecting 700 microspheres into the right internal carotid artery of rats [microsphere-embolized (ME) rats]. The ME and sham-operated rats were treated with 10 mg/kg/day nefiracetam p.o. from the first to the 9th day after the operation. The escape latency of the ME rat in the water maze test, when performed on days 7 to 9 after the operation, was lengthened. This effect was attenuated by the delayed treatment with nefiracetam. The nefiracetam-treated ME rat showed a shortened escape latency in the retention test on day 17 as well as in the contraposition test on day 18. These results indicate that a persistent improvement of the spatial memory function impaired by sustained cerebral ischemia was achieved even after cessation of treatment with nefiracetam. The functional damage to learning and memory was associated with decreases in the membranous adenylyl cyclase I and cytosolic protein kinase A (PKA) catalytic subunit and regulatory subunit proteins in the right hippocampus and cerebral cortex. The delayed treatment with nefiracetam appreciably prevented the decreases in these proteins. The present study suggests that nefiracetam may have an ability to cause persistent improvement of learning and memory function, possibly through protection against the ischemia-induced impairment to the adenylyl cyclase/cAMP/PKA signal transduction pathway.

Footnotes

  • DOI: 10.1124/jpet.102.043653

  • Abbreviations:
    AC
    adenylyl cyclase
    PKA
    protein kinase A
    ME
    microsphere-embolized/nefiracetam-untreated
    CREB
    cAMP responsive element-binding protein
    S
    nefiracetam-untreated sham-operated
    SN
    nefiracetam-treated sham-operated
    MN
    nefiracetam-treated microsphere-embolized
    ANOVA
    analysis of variance
    PLSD
    protected least significant difference
    • Received August 26, 2002.
    • Accepted October 1, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 304 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 304, Issue 2
1 Feb 2003
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Research ArticleNEUROPHARMACOLOGY

Persistent Effects of Delayed Treatment with Nefiracetam on the Water Maze Task in Rats with Sustained Cerebral Ischemia

Satoshi Takeo, Tomoko Fukatsu, Keiko Miyake-Takagi, Norio Takagi, Makiko Niimura, Akira Nagakura, Tsuyoshi Ando and Kouichi Tanonaka
Journal of Pharmacology and Experimental Therapeutics February 1, 2003, 304 (2) 513-523; DOI: https://doi.org/10.1124/jpet.102.043653

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Research ArticleNEUROPHARMACOLOGY

Persistent Effects of Delayed Treatment with Nefiracetam on the Water Maze Task in Rats with Sustained Cerebral Ischemia

Satoshi Takeo, Tomoko Fukatsu, Keiko Miyake-Takagi, Norio Takagi, Makiko Niimura, Akira Nagakura, Tsuyoshi Ando and Kouichi Tanonaka
Journal of Pharmacology and Experimental Therapeutics February 1, 2003, 304 (2) 513-523; DOI: https://doi.org/10.1124/jpet.102.043653
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