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Behavioral Pharmacology

開催日 2014/9/13
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Cilostazol, a phosphodiesterase 3 inhibitor, improves memories in senescence accelerated mice

  • P3-348
  • 遠藤 昌吾 / Shogo Endo:1 柳井 修一 / Shuichi Yanai:1 小島 開 / Kai Kojima:1 新崎 智子 / Tomoko Arasaki:1 
  • 1:東京都健康長寿医療センター研究所・老化脳神経科学 / Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan 

cAMP pathway plays an essential role on learning and memory through activating PKA-CREB system. cAMP is generated by adenylate cyclase and hydrolyzed by phosphodiesterases (PDEs). Thus, PDE inhibitors elevate intracellular cAMP concentration to ehnance cAMP actions. Inhibitors specific for PDE isoforms have been developed to treat diseases. One of these compounds, cilostazol, is a selective PDE3 inhibitor and is widely used as an antiplatelet drug. Recently, we reported that cilostazol enhanced hippocampus-dependent memory in young mice, however, its effects have not been examined for the age-related memory impairments. We examined the effect of cilostazol on conditioned fear memory in the senescence accelerated mouse prone 8 (SAM P8), which shows an early onset of memory impairment, considering possible clinical applications.
SAM P8 and the control normal aging mice (8-month old) were divided into the acute administration group and chronic administration group. For the acute administration group, cilostazol (0, 30, 100 mg/kg body weight) was orally administered 30 min prior to the experiments. In the chronic administration group, feed containing cilostazol (0, 30, or 1.5 %) had been administered for 3 months (5-8-month old). In the fear conditioning task, mice received single pairing of pure tone and 0.30 mA electric foot shock (conditioning). The cue-dependent memory and the context-dependent memory were examined 24 hrs and 48 hrs after the conditioning, respectively. No significant effect of cilostazol was observed on the conditioned freezing in the acute administered group. On the other hand, in the chronic administration group, 1.5% cilostazol-administered SAM P8 exhibited significantly higher performance than the non-cilostazol-administered SAM P8 group in both cue- and context-dependent memory tests. Performance of 1.5% cilostazol-administered SAM P8 was comparable to that of the control normal aging mice. The results suggest that chronic administration of cilostazol exerts memory improvement effects in both amygdala- and hippocampus-dependent memories.

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