Repeated electroconvulsive shock promotes the sprouting of serotonergic axons in the lesioned rat hippocampus

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.