Eplerenone, a selective mineralocorticoid receptor blocker, exerts anxiolytic effects accompanied by changes in stress hormone release.
The aim of this study was to investigate the impact of chronic treatment with eplerenone, a mineralocorticoid receptor antagonist and clinically used antihypertensive drug, on animal correlates of mood disorders, namely anxiety-like behaviour, stress hormones release and brain plasticity. Male rats (n = 40) were injected subcutaneously twice daily with eplerenone (50 mg/kg body weight) or vehicle for 11 days. Open-field and elevated plus-maze tests were used as both anxiety-related paradigms and stress stimuli to evaluate hormone responses. Eplerenone-treated rats showed reduced anxiety-like behaviour manifested by both conventional and ethological parameters related to exploration and risk assessment behaviour in the elevated plus-maze test and partially in the open-field test. Eplerenone treatment resulted in an elevation of plasma aldosterone and oxytocin levels. Chronic treatment with eplerenone prevented the stress-induced rise in plasma corticosterone levels and vasopressin concentrations in the posterior pituitary. Eplerenone treatment failed to induce substantial changes in hippocampal brain derived neurotrophic factor protein concentrations. In conclusions, chronic treatment with eplerenone (1) exerts anxiolytic effects and (2) influences corticosterone, oxytocin and vasopressin concentrations in a manner consistent with the anxiolytic outcome.
Hlavacova
Natasa
N
Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Bakos
Jan
J
Jezova
Daniela
D
D000302:Adrenal Cortex / Q000187:drug effects*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D000077545:Eplerenone; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009473:Neuronal Plasticity / Q000187:drug effects; D010121:Oxytocin / Q000097:blood / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013315:Stress, Psychological; D014667:Vasopressins / Q000097:blood / Q000378:metabolism
D014151:Anti-Anxiety Agents; D019208:Brain-Derived Neurotrophic Factor; D000451:Mineralocorticoid Receptor Antagonists; D014667:Vasopressins; D013148:Spironolactone; D000450:Aldosterone; D010121:Oxytocin; D000077545:Eplerenone; D003345:Corticosterone