Subchronic Treatment With Aldosterone Induces Depression-like Behaviors and Gene Expression Changes Relevant to Major Depressive Disorder


The potential role of aldosterone in the pathophysiology of depression is unclear. The aim of this study was to test the hypothesis that prolonged elevation of circulating aldosterone induces depression-like behavior accompanied by disease-relevant changes in gene expression in the hippocampus. Subchronic (2-wk) treatment with aldosterone (2 µg/100 g body weight per day) or vehicle via subcutaneous osmotic minipumps was used to induce hyperaldosteronism in male rats. All rats (n=20/treatment group) underwent a modified sucrose preference test. Half of the animals from each treatment group were exposed to the forced swim test (FST), which served both as a tool to assess depression-like behavior and as a stress stimulus. Affymetrix microarray analysis was used to screen the entire rat genome for gene expression changes in the hippocampus. Aldosterone treatment induced an anhedonic state manifested by decreased sucrose preference. In the FST, depressogenic action of aldosterone was manifested by decreased latency to immobility and increased time spent immobile. Aldosterone treatment resulted in transcriptional changes of genes in the hippocampus involved in inflammation, glutamatergic activity, and synaptic and neuritic remodeling. Furthermore, aldosterone-regulated genes substantially overlapped with genes affected by stress in the FST. This study demonstrates the existence of a causal relationship between the hyperaldosteronism and depressive behavior. In addition, aldosterone treatment induced changes in gene expression that may be relevant to the aetiology of major depressive disorder. Subchronic treatment with aldosterone represents a new animal model of depression, which may contribute to the development of novel targets for the treatment of depression.

Authors: Natasa Hlavacova, Paul D. Wes, Maria Ondrejcakova, Marianne E. Flynn, Patricia K. Poundstone, Stanislav Babic, Harald Murck, Daniela Jezova
Keywords: aldosterone, behavior, depression, gene expression profiling, stress
DOI Number: 10.1017/S1461145711000368      Publication Year: 2012

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