催产素对甲基苯丙胺引起的小鼠前额叶皮层和海马内N-甲基-D-天冬氨酸受体亚型1蛋白表达变化的影响

Effects of oxytocin on changes of N-methyl-D-aspartate receptor 1 expression in prefrontal cortex and hippocampus of mice induced by methamphetamine

目的研究脑室注射催产素对甲基苯丙胺引起的小鼠前额叶皮层和海马内谷氨酸N-甲基-D-天冬氨酸受体亚型1(NMDAR1)蛋白表达变化的影响,为探讨催产素拮抗甲基苯丙胺精神依赖作用的中枢机制提供实验依据。方法分别取经急性和慢性甲基苯丙胺处理的小鼠的前额叶皮层和海马,采用Western Blot分析方法检测催产素对NMDAR1蛋白表达的影响。结果催产素可以显著拮抗急性给予甲基苯丙胺及复吸甲基苯丙胺引起的小鼠前额叶皮层NMDAR1蛋白表达的增高;可以显著抑制甲基苯丙胺戒断时引起的小鼠前额叶皮层NMDAR1蛋白表达的降低;急性及慢性甲基苯丙胺处理对小鼠海马内NMDAR1蛋白表达没有显著性影响。结论用甲基苯丙胺处理对小鼠前额叶皮层部位NMDAR1蛋白表达的影响较大;催产素可以拮抗甲基苯丙胺引起的前额叶皮层部位NMDAR1蛋白表达的变化。

Objective To investigate the effects of intracerebroventricular injection of oxytocin on methamphetamine-induced changes of N-methyi-D-aspartate receptor 1 （NMDAR1） expression in prefrontal cortex and hippocampus of mice. Methods Western blot analysis was used to determine the influence of oxytocin on protein expression of NMDAR1 during different phases of methamphetamine administration. Results Oxytocin significantly inhibited the increase of NMDAR1 levels in prefrontal cortex induced by methamphetamine acute administration and methamphetamine-challenging relapse. Moreover, oxytocin markedly attenuated the decrease of NMDAR1 levels in prefrontal cortex induced by methamphetamine withdrawal. No significant difference of NMDAR1 expression was observed in hippocampus of mice after treatment with methamphetamine. Conclusions NMDAR1 subunits in prefrontal cortex are more sensitive to methamphetamine administration than those in hippocampus. Oxytocin significantly antagonizes the changes of NMDAR1 expression induced by methamphetamine in prefrontal cortex of mice.