Madhav T R, Pei Q, Grahame-Smith D G, Zetterström T S
Oxford University-SmithKline Beecham Centre for Applied Neuropsychobiology, University Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, OX2 6HE, Oxford, UK.
Neuroscience. 2000;97(4):677-83. doi: 10.1016/s0306-4522(00)00083-x.
This study reports the effect of repeated electroconvulsive shock on the sprouting of 5-hydroxytryptamine neurons in the partly lesioned rat dorsal hippocampus. We have adopted a 5-hydroxytryptamine homotypic collateral sprouting model to examine whether electroconvulsive shock administration altered the rate of 5-hydroxytryptamine axonal reinnervation of the dorsal hippocampus. The 5-hydroxytryptamine innervation of hippocampus originates from the median raphe via the cingulum bundle and the fimbria-fornix. Lesioning of the cingulum bundle has previously been shown to cause sprouting of intact 5-hydroxytryptamine afferents originating from the unharmed fimbria-fornix. Rats were unilaterally injected with the 5-hydroxytryptamine neurotoxin, 5,7-dihydroxytryptamine, into the right cingulum bundle and 5-hydroxytryptamine immunoreactivity in the dorsal hippocampus was investigated 1, 3, 6 and 12weeks after the injection. The lowest level of 5-hydroxytryptamine-immunoreactivity in the hippocampus was detected at three weeks after the lesion. At six weeks, 5-hydroxytryptamine immunoreactive fibres started to reappear, and at 12weeks the level of 5-hydroxytryptamine immunoreactivity was similar to that observed on the unlesioned side. Based on this time-course, six weeks was chosen as the time-point to investigate the action of a course of repeated electroconvulsive shock administrations. Repeated electroconvulsive shock (five shocks over 10days) doubled the number of sprouting 5-hydroxytryptamine-immunoreactive fibres and significantly increased levels of the 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid. The present data provide the first direct evidence that electroconvulsive shock enhances 5-hydroxytryptamine axon sprouting in the partly lesioned hippocampus. This is an effect which may contribute to the therapeutic effect of electroconvulsive therapy in major depression.
本研究报告了重复电惊厥休克对部分损伤的大鼠背侧海马中5-羟色胺神经元发芽的影响。我们采用了5-羟色胺同型侧支发芽模型，以检查给予电惊厥休克是否改变了背侧海马中5-羟色胺轴突再支配的速率。海马的5-羟色胺神经支配起源于中缝核，通过扣带束和穹窿-海马伞。先前已表明，扣带束损伤会导致源自未受损穹窿-海马伞的完整5-羟色胺传入纤维发芽。将大鼠右侧扣带束单侧注射5-羟色胺神经毒素5,7-二羟色胺，并在注射后1、3、6和12周研究背侧海马中的5-羟色胺免疫反应性。在损伤后三周检测到海马中5-羟色胺免疫反应性的最低水平。在六周时，5-羟色胺免疫反应性纤维开始重新出现，在12周时，5-羟色胺免疫反应性水平与未损伤侧观察到的相似。基于这个时间进程，选择六周作为研究重复电惊厥休克给药疗程作用的时间点。重复电惊厥休克（10天内给予五次电击）使发芽的5-羟色胺免疫反应性纤维数量增加了一倍，并显著提高了5-羟色胺代谢物5-羟吲哚乙酸的水平。目前的数据提供了首个直接证据，表明电惊厥休克可增强部分损伤海马中的5-羟色胺轴突发芽。这一效应可能有助于解释电惊厥疗法在重度抑郁症中的治疗效果。
