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Research ArticleNEUROPHARMACOLOGY

Effects of T-588, a Cognitive Enhancer Compound, on Synaptic Plasticity in the Dentate Gyrus of Freely Moving Rats

Hidetoshi Yamaguchi, Ryoi Tamura, Jun-Ichi Kuriwaki, Satoshi Eifuku and Taketoshi Ono
Journal of Pharmacology and Experimental Therapeutics July 2001, 298 (1) 354-361;
Hidetoshi Yamaguchi
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Ryoi Tamura
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Jun-Ichi Kuriwaki
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Satoshi Eifuku
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Taketoshi Ono
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Abstract

(1R)-1-benzo [b] thiophen-5-yl-2-[2-(diethylamino) ethoxy] ethan-1-ol hydrochloride (T-588) is a compound for the treatment of neurodegenerative disorders, including Alzheimer's disease and cerebrovascular diseases. T-588 reportedly alleviates learning and memory deficits in animal models of dementia. In the present study, we investigated the effects of T-588 on the induction and decay of long-term potentiation (LTP) and on the responses to paired-pulse (pp) stimulation in freely moving rats. Perforant path-evoked field potentials were recorded in the dentate gyrus by chronically implanted electrodes. LTP was induced by high-frequency stimulation 30 min after oral administration of T-588 (0.3 or 3 mg/kg). T-588 significantly augmented the increase in population spike amplitude and field excitatory postsynaptic potential slope after LTP induction. T-588 also prolonged the decay of augmented population spike amplitude, but had no significant effect on the response to pp stimulation. These results suggest that T-588 facilitates long-term synaptic plasticity, but not short-term synaptic plasticity in the dentate gyrus of freely moving rats. The effect of T-588 on long-term synaptic plasticity may contribute to the alleviation of learning and memory dysfunction seen in animal models.

Footnotes

  • ↵1 Present address: Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1 Shimo-okui, Toyama 930-8508, Japan.

  • This work was partly supported by Grants-in-Aid for Scientific Research on Priority Areas (A)-Research for Comprehensive Promotion of Study of Brain (12050220), Priority Areas (C)-Advanced Brain Science Project (12210009), and Scientific Research (11308033 and 11680805)-from Ministry of Education, Culture, Sports, Science and Technology, Japan.

  • Abbreviations:
    T-588
    (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride
    ACh
    acetylcholine
    NA
    noradrenaline
    LTP
    long-term potentiation
    DG
    dentate gyrus
    PS
    population spike
    fEPSP
    field excitatory postsynaptic potential
    IPI
    interpulse interval
    I/O
    input/output
    IRI
    inter-recording interval
    HFS
    high-frequency stimulation
    EPSP
    excitatory postsynaptic potential
    ANOVA
    analysis of variance
    E-S
    EPSP spike
    GABA
    γ-aminobutyric acid
    • Received January 2, 2001.
    • Accepted March 26, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 1
1 Jul 2001
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Research ArticleNEUROPHARMACOLOGY

Effects of T-588, a Cognitive Enhancer Compound, on Synaptic Plasticity in the Dentate Gyrus of Freely Moving Rats

Hidetoshi Yamaguchi, Ryoi Tamura, Jun-Ichi Kuriwaki, Satoshi Eifuku and Taketoshi Ono
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 354-361;

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Research ArticleNEUROPHARMACOLOGY

Effects of T-588, a Cognitive Enhancer Compound, on Synaptic Plasticity in the Dentate Gyrus of Freely Moving Rats

Hidetoshi Yamaguchi, Ryoi Tamura, Jun-Ichi Kuriwaki, Satoshi Eifuku and Taketoshi Ono
Journal of Pharmacology and Experimental Therapeutics July 1, 2001, 298 (1) 354-361;
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