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Journal of Neural Transmission

, Volume 108, Issue 8–9, pp 1065–1079 | Cite as

Memory deficits and increased emotionality induced by β-amyloid (25–35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus

  • A. Olariu
  • M. H. Tran
  • K. Yamada
  • M. Mizuno
  • V. Hefco
  • T. Nabeshima

Summary.

In the present study we found that chronic infusion of β-amyloid fragment (25–35) at nanomolar concentration into rat cerebral ventricle impairs learning and memory. At a concentration of 3 nmol/day but not 0.3 nmol/day, β-amyloid significantly reduced the spontaneous alternation behavior and the memory performance in the water maze and multiple passive avoidance tests. A significant increase in anxiety was also found in the animals infused with 3 nmol/day β-amyloid fragment. Memory deficits and the increased emotionality were correlated with a decreased nicotine-evoked acetylcholine release from the frontal cortex/hippocampus, as assessed by microdialysis, in freely moving rats. The amyloid fragment infused either at pico- or nanomolar concentrations reduced the affinity of [3H] phorbol dibutyrate binding, an index of activated protein kinase C (PKC), and increased the total number of binding sites in the hippocampal particulate fraction. Our results suggest that the amnesic and anxiogenic effects of chronic infusion of β-amyloid (25–35) are related to the decreased acetylcholine release and reduced PKC activation.

Keywords: Memory impairment, emotional behavior, β-amyloid, cholinergic deficit, protein kinase C (PKC). 

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Copyright information

© Springer-Verlag Wien 2001

Authors and Affiliations

  • A. Olariu
    • 1
  • M. H. Tran
    • 1
  • K. Yamada
    • 1
  • M. Mizuno
    • 1
  • V. Hefco
    • 2
  • T. Nabeshima
    • 1
  1. 1.Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, JapanJP
  2. 2.Department of Animal Physiology, Faculty of Biology, “Alexandru Ioan Cuza” University, Iasi, RomaniaRO

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