Effect of single treatment with the antihypertensive drug eplerenone on hormone levels and anxiety-like behaviour in rats.

Hlavacova, Natasa; Jezova, Daniela

OBJECTIVE The aim of the study was to investigate the effects of single peripheral administration of mineralocorticoid receptor (MR) antagonist eplerenone on: 1. the hypothalamic-pituitary-adrenocortical (HPA) axis; 2. the renin-angiotensin-aldosterone (RAA) system, 3. anxiety-like behaviour. METHODS Male Wistar rats were injected subcutaneously with eplerenone (100 mg/kg body weight) or vehicle. Two hours following the injections, a half of the animals from each treatment group were decapitated to obtain blood for measurement of hormone levels. The other half of the animals was subjected to behavioural testing in the elevated plus-maze test. To provide comprehensive behavioural profile of eplerenone, standard spatiotemporal and ethologically derived measures of anxiety were assessed. RESULTS Single treatment with eplerenone resulted in a significant increase in plasma aldosterone levels. Plasma concentrations of ACTH and corticosterone were not modified by eplerenone injection. Administration of eplerenone failed to alter classical spatiotemporal measures of anxiety (number of entries and time spent in the open arms). However, ethological parameters related to exploration (head dipping) and risk assessment behaviour (stretched attend postures) were significantly affected by eplerenone injection. CONCLUSIONS Single injection of eplerenone is followed by a reduction of ethological indices of anxiety-like behaviour and by an elevation of plasma aldosterone levels. Acute administration of eplerenone appears to affect the RAA system but not hormones of the HPA axis.