Background: Electroconvulsive therapy (ECT) is a widely used and efficient treatment modality in psychiatry

From clinical studies it is known that recurrent depressive episodes associate with a reduced hippocampal volume. Conversely, preclinical studies have shown that chronic antidepressant treatment increases hippocampal neurogenesis. Consequently, it has been suggested that a deficit in hippocampal neurogenesis is implicated in the pathophysiology of depression. To study a potential correlation between recovery and hippocampal cytogenesis, we established the chronic mild stress (CMS) rat model of depression. When rats are subjected to CMS, several depressive symptoms develop, including the major symptom anhedonia. Rats were exposed to stress for 2 weeks and subsequently to stress in combination with antidepressant treatment for 4 consecutive weeks. The behavioral deficit measured in anhedonic animals is a reduced intake of a sucrose solution. Prior to perfusion animals were injected with bromodeoxyuridine (BrdU), a marker of proliferating cells. Brains were sectioned horizontally and newborn cells positive for BrdU were counted in the dentate gyrus and tracked in a dorsoventral direction.CMS significantly decreased sucrose consumption and cytogenesis in the ventral part of the hippocampal formation. During exposure to the antidepressant escitalopram, given as intraperitoneally dosages of either 5 or 10 mg/kg/ day, animals distributed in a bimodal fashion into a group, which recovered (increase in sucrose consumption), and a subgroup, which refracted treatment (no increase in sucrose consumption). Chronic treatment with escitalopram reversed the CMS-induced decrease in cytogenesis in the dentate gyrus of the ventral hippocampal formation, but in recovered animals only. Our data show a correlation between recovery from anhedonia, as measured by cessation of behavioral deficits in the CMS model, and an increase in cytogenesis in the dentate gyrus of the ventral hippocampal formation.

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Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. Link to publication Citation for published version (APA): Hellsten, J., Wennström, M., Mohapel, P., Ekdahl Clementson, C., Bengzon, J., & Tingström, A. (2002). Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. European Journal of Neuroscience, 16(2), 283-290. DOI: 10.1046/j.1460-9568.2002 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractMajor depression is often associated with elevated glucocorticoid levels. High levels of glucocorticoids reduce neurogenesis in the adult rat hippocampus. Electroconvulsive seizures (ECS) can enhance neurogenesis, and we investigated the effects of ECS in rats where glucocorticoid levels were elevated in order to mimic conditions seen in depression. Rats given injections of corticosterone or vehicle for 21 days were at the end of this period treated with either a single or ®ve daily ECSs. Proliferating cells were labelled with bromodeoxyuridine (BrdU). After 3 weeks, BrdU-positive cells in the dentate gyrus were quanti®ed and analyzed for co-labelling with the neuronal marker neuron-speci®c nuclear protein (NeuN). In corticosterone-treated rats, neurogenesis was decreased by 75%. This was counteracted by a single ECS. Multiple ECS further increased neurogenesis and no signi®cant differences in BrdU/NeuN positive cells were detected between corticosterone-and vehicle-treated rats given ®ve ECS. Approximately 80% of the cells within the granule cell layer and 10% of the hilar cells were double-labelled with BrdU and NeuN. We therefore conclude that electroconvulsive seizures can increase hippocampal neurogenesis even in the presence of elevated levels of glucocorticoids. This further supports the hypothesis that induction of neurogenesis is an important event in the action of antidepressant treatment.

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