2P260 Delayed treatment with nefiracetam improved the water maze task of the rats with microsphere embolism

• Published in: Journal of Pharmacological Sciences 2003, Vol.91 (suppl.1), p.188-188
• Main Authors: Tsuyoshi Ando, Tomoko Fukatsu, Keiko Miyake-Takagi, Norio Takagi, Makiko Niimura, Akira Nagakura, Kouichi Tanonaka, Satoshi Takeo
• Format: Article
• Language: Japanese
• ISSN: 1347-8613

The aim of the present study was to determine whether nefiracetam (NeD might have a persistent recognition-enhancing effect in animals with sustained cerebral ischemia. Cerebral ischemia was induced by injecting 700 microspheres into the right internal carotid artery of rats (ME rats). The animals were treated with 10 mg/kg/day Nef p. o. from the I st to the 9th day after the operation. In the ME rat, the escape latency in the water maze task when performed on days 7 to 9 after operation was prolonged. This effect was attenuated by the delayed treatment with Nef. The Nef-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. The ME rat showed decreases in the membranous adenylyl cyclase I and cytosolic PKA catalytic and regulatory subunit proteins in the ipsilateral hippocampus and cerebral cortex. Treatment with Nef prevented the decreases in these proteins. The present study suggests that Nef may have an ability to cause persistent improvement of spatial memory function possibly through protection against the ischemia-induced impainnent of the adenylyl cyclase/cAMP/PKA pathway.