(-),(+)黄皮酰胺对樟柳碱引起的小鼠脑内乙酰胆碱含量降低及记忆障碍的影响

为证实黄皮酰胺体内抗记忆缺失作用是否也存在手性选择性,并且进一步探讨其作用的机制,用高效液相色谱 电化学检测器法测定乙酰胆碱含量并结合行为学实验,比较了(-),(+)黄皮酰胺对小鼠脑内乙酰胆碱含量及对小鼠记忆障碍的影响。结果表明:(-)黄皮酰胺剂量依赖性地对抗樟柳碱引起的脑皮层、海马、纹状体内乙酰胆碱含量降低,(+)黄皮酰胺在同样剂量却无此作用。行为学实验也得到相似结果。提示:黄皮酰胺的药理作用存在手性选择性;(-)黄皮酰胺能改善樟柳碱所致的记忆障碍,这与其逆转樟柳碱引起的脑内乙酰胆碱含量降低作用相关。

EFFECTS OF (-), (+)CLAUSENAMIDE ON ANISODINE-INDUCED ACETYLCHOLINE DECREASE AND ASSOCIATED MEMORY DEFICITS IN THE MOUSE BRAIN

The effect of a new cognition enhancer clausenamide on regional acetylcholine (ACh) levels and anisodine-induced ACh decrease were examined in mice of memory deficits. In the mean time, the effect of (-)clausenamide on ACh was compared with that of (+)clausenamide. Animal amnesia model was induced by i.p. anisodine, brain acetylcholine content was measured by high performance liquid chromatography with electrochemical detection. It was found that single administration of (-)clausenamide or (+)clausenamide(10, 20, 50 mg.kg-1, ig) showed no effect on the ACh level in the frontal cortex, hippocampus and striatum in normal condition. However, pretreatment with (-)clausenamide (10, 20, 50 mg.kg-1, ig) significantly ameliorated the reduction of ACh in these regions induced by anisodine (10 mg.kg-1, i.p.) in a dose-dependent manner. In the meantime, (-) clausenamide ameliorate anisodine-induced memory deficits in step-through test in mice. In contrast, (+)clausenamide showed no effect on these sides. The results indicate that there is significant difference between the actions of (-)clausenamide and (+)clausenamide; The protective action of (-)clausenamide against anisodine-induced amnesia is due to its ability to reverse ACh reduction.