Studies of the Protective Effects of Paeoniflorin on Drug-Induced Central Excitatory Behavior

• Main Authors: Hsun-Lang Fang, 方焄蓮
• Other Authors: Yuh-Fung Chen
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/04169367293473547276

碩士 === 中國醫藥學院 === 醫學研究所 === 88 === Paeoniae radix has been used to relieve spasmodic abdominal pain. Paeoniflorin, a major component from Paeonia lactifloria, has several pharmacological effects including antiallergic, antinociceptive, antispasmodic and anti-inflammatory actions. In our previous studies, we found that paeoniflorin had antinociceptive effect on both formalin test and writhing response. In this study, we tried to investigate the effect of paeoniflorin on drug-induced central excitatory behavior. Effect of paeoniflorin (48, 96, 240 g / 5l i.c.v.) alone or coadministered with glutamate receptor antagonists (MK-801, AP5, NBQX i.t.) on intrathecal administration of different drug-induced central excitatory behavior were studied. Drugs (NMDA, AMPA, glutamate, strychnine and substance P etc.) agonist intrathecally administered evoked scratching and biting behavior, whereas, glutamate receptor antagonists attenuated scratching and biting behavior induced by glutamate receptor agonists. The effect of glutamate receptor antagonists on drug-induced central excitatory behavior was potentiated by co-administration of paeoniflorin. The results revealed the effect of glutamate receptor antagonists was potentiated by paeoniflorin. To test the involvement of paeoniflorin in the drugs induced excitatory behaviors on NMDA receptor, the effects of an antisense oligodeoxynucleotide against (NR1, 2A, 2B, and 2C) on the NMDA and high dose morphine induced excitatory behaviors were studied. The results of intrathecal treatment once daily antisense oligodeoxy-nucleotides significantly attenuated high dose morphine induced excitatory behavior on day1, on day 3 and 7, significantly attenuated NMDA induced excitatory behavior. The effect of antisense oligodeoxynucleotide on drug-induced central excitatory behavior was potentiated by co-administration of paeoniflorin. Furthermore, from the results of immunohistochemical detection of NMDA receptor in mice brain cortex. These immunohistochemistry and western blot results were consistent with our conclusions that the behavioral effects of the NMDA receptor antisense oligodeoxynucleotide did result from the downregulation of the NMDA receptors by antisense oligodeoxy-nucleotide. From our results, it was suggested that the effect of paeoniflorin on drug-induced central excitatory behavior might via the inactivation of NMDA receptor.