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目的 从齿状回长时程增强效应 (LTP)方面研究锂的治疗作用机理。方法 细胞外记录离体海马脑片神经元兴奋性突触后电位 (EPSP)。结果锂可逆地增强EPSP的幅度。高频刺激 (10 0Hz ,1s)对照组大鼠海马穿通纤维 ,在海马齿状回 (DG)区记录的EPSP幅度会持续增高 ,可以诱导出明显的突触后LTP。若用 10mmol·L- 1锂处理大鼠海马脑片 ,则诱导的LTP幅度明显降低 ,但低浓度锂 (2 ,6mmol·L- 1)不影响LTP的幅度 ;10mmol·L- 1锂明显抑制海马脑片DG区的脉冲间隔 (IPI)为 5 0ms的双脉冲易化效应 (PPF) ,而低浓度锂 (2 ,6mmol·L- 1)处理则不影响PPF(IPI,5 0ms) ;在不同的细胞外钙浓度下 ,用 10mmol·L- 1锂处理过的海马脑片PPF受到的抑制程度不同。结论 锂可能通过突触前的机理来抑制海马DG区LTP的幅度 ,这种抑制效应与锂的临床治疗狂躁症及其副作用之间的关系尚需进一步的研究。
Objective To study the therapeutic mechanism of lithium treatment from dentate gyrus long-term potentiation (LTP). Methods The excitatory postsynaptic potential (EPSP) of neurons in isolated hippocampal slices was recorded extracellularly. Lithium reversibly increases the magnitude of EPSP. High-frequency stimulation (10 0 Hz, 1 s) hippocampus perforation fibers in the hippocampal dentate gyrus (DG) region recorded a continuous increase in amplitude, can induce significant postsynaptic LTP. When treated with 10mmol·L-1 lithium, the amplitude of LTP was significantly decreased, while the low concentration of lithium (2, 6mmol·L-1) did not affect the amplitude of LTP. Lithium 10mmol·L-1 was significantly inhibited The pulse interval (IPI) in hippocampal slices DGD was 5 ms PPF, while low concentration lithium (6 mmol·L -1) did not affect PPF (IPI 5 ms) Different concentrations of extracellular calcium, 10mmol·L-1 lithium treatment of hippocampal slices of PPF by different degrees of inhibition. Conclusion Lithium may inhibit the amplitude of LTP in DG area of hippocampus through presynaptic mechanism. The relationship between this inhibitory effect and the clinical treatment of manic disorder and its side effects needs further study.