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- 2018
激活或阻断内侧隔斜角带复合体中5-HT1A受体对帕金森病模型大鼠认知功能的影响
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Abstract:
摘要：目的 探讨内侧隔斜角带复合体(medial septum-diagonal band of Broca complex, MS-DB)中5-HT1A受体在帕金森病(Parkinson’s disease, PD)认知功能中的作用及机制。方法 以6-羟基多巴胺(6-hydroxydopamine, 6-OHDA)损毁单侧内侧前脑束(medial forebrain bundle, MFB)的PD模型大鼠为对象，采用行为学和电生理学方法，观察激活或阻断MS-DB中5-HT1A受体对PD认知功能和海马theta节律的影响。结果 ①单侧MFB损毁降低了大鼠在T-迷宫实验中的选择正确率，MS-DB局部注射5-HT1A受体激动剂8-OH-DPAT进一步降低模型组大鼠在T-迷宫实验中的选择正确率，而MS-DB局部注射选择性5-HT1A受体拮抗剂WAY100635升高模型组大鼠的选择正确率；②单侧MFB损毁使海马theta节律的峰频率降低，MS-DB局部注射8-OH-DPAT抑制海马theta节律，降低theta节律的标准化功率，而MS-DB局部注射WAY100635诱发海马theta节律，并使theta节律的标准化功率升高。结论 阻断MS-DB中的5-HT1A受体可改善模型组大鼠的工作记忆，这可能是通过兴奋海马theta节律来实现的。
ABSTRACT: Objective To explore the role and mechanisms of 5-HT1A receptors in the medial septum-diagonal band of Broca complex (MS-DB) in hemiparkinsonian rats. Methods Combined behavioral and electrophysiological studies were performed to assess the role of MS-DB 5-HT1A receptors in working memory and hippocampal theta rhythm in rats with 6-hydroxydopamine (6-OHDA) lesions in the medial forebrain bundle (MFB). Results ① MFB lesions in the rats decreased choice accuracy in the T-maze rewarded alternation test. Intra-MS-DB injection of 5-HT1A receptor agonist 8-OH-DPAT further decreased choice accuracy, while intra-MS-DB injection of 5-HT1A receptor antagonist WAY-100635 increased choice accuracy in the lesioned rats. ② MFB lesions in the rats decreased peak theta rhythm frequency. Intra-MS-DB injection of 8-OH-DPAT suppressed hippocampal theta rhythm and decreased normalized theta power, while intra-MS-DB injection of WAY-100635 induced theta rhythm and increased normalized theta power. Conclusion Blockade of MS-DB 5-HT1A receptors can recover cognitive dysfunction in Parkinson’s disease, which may be attributed to the enhancement of hippocampal theta rhythm
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