伏隔核区D-丝氨酸调节可卡因成瘾行为-神经病学专业论文.docx

PAGE PAGE IV Abstract exogenous D-serine blocked the development of behavioral sensitization in a dose-dependent manner[one-way ANOVA; F(3，44) = 33.65， P 0.01 ； F(3，20) = 13.25,P 0.01; respectively]. Western blot showed pCREB and pERK1/2 levels significantly increased in NAc of behavioral sensitization rats(P 0.05)，but CaMKII phosphorylation levels did not show any significant effects after drug administration(P ﹥ 0.05). And electrophysiological methods showed that D-serine was essential for NMDAR-LTD in NAc and exogenous D-serine regulated NMDAR-LTD in a bell-shaped concentration-dependent manner. We also found that NMDAR-LTD in NAc was disrupted of chronic cocaine-treated rats. Conclusion: The D-serine deficit observed in NAc of cocaine-treated rats is likely due to the altered amount of key enzyme.Exogenous D-serine blocks the development of behavioral sensitization， so， D-serine may be an effective therapeutic agent for cocaine addiction.The ERK-CREB-Fos pathway involves in cocaine-induced behavioral sensitization.NMDAR-LTD of cortico-accumbal glutamatergic synapse is disrupted in chronic cocaine-treated rats and reversed by D-serine. Keywords: nucleus accumbens; D-serine; behavioral sensitization; cocaine. 目录 目录 PAGE PAGE V 目 录 第 1 章 前言 1 第 2 章 材料与方法 4 2.1 实验动物 4 2.2 主要药品和试剂 4 2.3 自配试剂 5 2.4 主要仪器 6 第 3 章 实验方法 8 3.1 不同浓度的可卡因建立的行为敏化模型鼠伏隔核 D-丝氨酸浓度及 SR、 DAAO 的表达变化 8 3.1.1 实验分组 8 3.1.2 采用 HPLC 技术测定伏隔核区 D-丝氨酸浓度 8 3.1.3 采用 Western blot 技术观察伏隔核区丝氨酸消旋酶及 D-氨基酸氧 化酶表达变化