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Galantamine and donepezil differently affect isolation rearing-induced deficits of prepulse inhibition in mice

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Abstract

Rationale

Previous studies have shown that alterations in acetylcholine (ACh) receptor subtypes might contribute to cognitive impairment observed in schizophrenia and that choline acetyltransferase activity in the parietal cortex is negatively correlated with the severity of such cognitive impairment. However, clinical data suggest that the acetylcholinesterase (AChE) inhibitors galantamine and donepezil have different effects on negative and cognitive symptoms in schizophrenia. Prepulse inhibition (PPI) deficits—sensory information-processing deficits observed in schizophrenia—may be useful models for studying the efficacy of AChE inhibitors as cognitive enhancers.

Objectives

The present study examined the effects of galantamine and donepezil on PPI deficits induced by an environmental factor and drugs.

Materials and methods

In the isolation-rearing model, 3-week-old male ddY mice were housed either in groups of five or six per cage or isolated in cages of the same size for more than 6 weeks. In the drug-induced model, apomorphine 1 mg/kg and MK-801 0.2 mg/kg were administered to 9- to 10-week-old male ddY mice.

Results

In isolation-reared mice, galantamine attenuated PPI deficits, while donepezil did not. Galantamine and donepezil both attenuated PPI deficits induced by apomorphine, but not by MK-801. The galantamine-induced improvements in PPI deficits were not prevented by the nicotinic ACh receptor antagonists mecamylamine and methyllycaconitine.

Conclusions

These observations suggest that galantamine and donepezil have different effects on the environmentally induced PPI deficits and that these observations may be relevant to the different effects of these drugs observed clinically in schizophrenia.

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Acknowledgments

This study was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, and from Janssen Pharmaceutical K.K.

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Authors and Affiliations

  1. Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Ken Koda, Yukio Ago, Toshiyuki Kawasaki & Toshio Matsuda

  2. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Hitoshi Hashimoto & Akemichi Baba

  3. Department of Experimental Disease Model, The Osaka–Hamamatsu Joint Research Center For Child Mental Development, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Hitoshi Hashimoto & Toshio Matsuda

Authors
  1. Ken Koda
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  2. Yukio Ago
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  3. Toshiyuki Kawasaki
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  4. Hitoshi Hashimoto
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  5. Akemichi Baba
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  6. Toshio Matsuda
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Corresponding author

Correspondence to Toshio Matsuda.

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Koda, K., Ago, Y., Kawasaki, T. et al. Galantamine and donepezil differently affect isolation rearing-induced deficits of prepulse inhibition in mice. Psychopharmacology 196, 293–301 (2008). https://doi.org/10.1007/s00213-007-0962-1

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  • DOI: https://doi.org/10.1007/s00213-007-0962-1

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