Chronic treatment with the mineralocorticoid hormone aldosterone results in increased anxiety-like behavior

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Horm Behav. 2008 Feb 21 [Epub ahead of print]

Chronic treatment with the mineralocorticoid hormone aldosterone results in

increased anxiety-like behavior.

Hlavacova N, Jezova D.

Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental

Endocrinology, Slovak Academy of Sciences, Vlarska 3,

833 06, Bratislava, Slovakia.

Aldosterone is the last component of the renin-angiotensin-aldosterone system

inducing its peripheral effects via mineralocorticoid

receptors (MR). Brain MR bind preferentially glucocorticoids. So far, the role

of MR in behavioral functions has been investigated

almost exclusively in relation to glucocorticoids. Recently, aldosterone itself

has been linked to affective disorders. The aim of

this study was to test the hypothesis that chronic elevation of circulating

levels of aldosterone leads to increased anxiety. We

have investigated the effects of chronic aldosterone treatment on (1)

anxiety-like behavior, and (2) basal and stress-induced levels

of selected hormones. Forty male Wistar rats were subcutaneously implanted with

osmotic minipumps and treated with aldosterone (2

microg/100 g/day) or vehicle for two weeks. Aldosterone concentrations in plasma

showed a mild (approximately four-fold) increase at

the end of two-week aldosterone treatment. This mild hyperaldosteronism resulted

in a significant enhancement of anxiety as

demonstrated by alterations in all indicators of anxiety-like behavior measured

in the open field and elevated plus-maze tests,

without significant changes in measures of general locomotor activity.

Aldosterone treatment affected not only the spatiotemporal

measures of anxiety, but also the ethological parameters related to exploration

and risk assessment. Chronic treatment with

aldosterone was associated with increased water intake and decreased plasma

renin activity, but failed to modify basal or

stress-induced activity of the hypothalamic-pituitary-adrenocortical axis. The

results provide evidence on anxiogenic action of

prolonged increase in circulating aldosterone concentrations. Thus, aldosterone

may represent an important target for future

antidepressant and anxiolytic drug development.

PMID: 18377905 [PubMed - as supplied by publisher]