甲基苯丙胺神经兴奋性作用新机制

来源 :第十六届全国神经精神药理学学术会议 | 被引量 : 0次 | 上传用户:apzhc
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  目的 探讨超极化激活、环核苷酸门控性离子通道(HCN)与甲基苯丙胺兴奋性作用之间的关系.方法 采用大鼠海马脑片和全细胞记录技术,观察甲基苯丙胺对神经元动作电位发放和HCN通道的作用.在甲基苯丙胺急性给药模型上,观察了甲基苯丙胺对HCN通道表达的影响,以及HCN通道拮抗剂ZD7288对模型动物刻板行为的影响.结果 甲基苯丙胺可以增大海马神经元HCN通道电流,并使神经元的动作电位发放频率明显增加.HCN通道拮抗剂ZD7288可以逆转甲基苯丙胺增大HCN通道电流和神经元动作电位发放频率的兴奋性作用.在大鼠腹腔注射甲基苯丙胺急性和亚急性动物模型上,发现大鼠海马、前额叶皮质、伏隔核、纹状体等脑区神经元上HCN1通道的表达明显上调.侧脑室注射ZD7288后,注射甲基苯丙胺的模型动物所表现出的摇头、转圈、后退等刻板行为得到明显改善.结论 在甲基苯丙胺引起的中枢兴奋性效应中,HCN通道发挥了重要作用,并与甲基苯丙胺导致的动物刻板行为相关.
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