Consequences of Early Postnatal Blockade of Aldosterone Synthesis on Behaviour and Stress Response in Male and Female Rats

Abstract

AimThe aim of the present study was to determine whether pharmacological inhibition of aldosterone synthesis during the stress-hyporesponsive period (SHRP) affects behaviour and adrenocortical stress responsiveness later in development and whether these effects differ between males and females. MethodsNewborn Wistar rat pups (males n=40, females n=40) were treated with aldosterone synthase inhibitor FAD286 (30 mg/kg per day, orally) or vehicle from PND3 to PND9. To verify the pharmacodynamic action of FAD286, serum and adrenal glands from 10-day-old pups were analysed. The remaining pups were weaned on PND21 and underwent open-field (PND23), elevated plus-maze (PND29) and salt-preference testing. At PND46, half of each group was exposed to restraint stress for 120 min. ResultsIn 10-day-old pups, treatment with FAD286 resulted in increased gene expression of CYP11B2 (aldosterone synthase) and CYP11B1 (11-beta-hydroxylase) in the adrenal glands, increased serum levels of corticosterone, and decreased concentrations of serum aldosterone. FAD286 did not modify the general locomotor activity assessed in juvenile rats. Inhibition of aldosterone synthase by FAD286 resulted in altered anxiety-like behaviour in a sex-dependent manner. Postnatal FAD286 treatment led to increased anxiety-like behaviour in female, but not male rats. During adolescence, early FAD286 treatment increased overall aldosterone concentrations without altering the aldosterone response to restraint. Basal corticosterone concentrations were unchanged, whereas the response to restraint was enhanced. ConclusionsThe present study demonstrates that transient inhibition of aldosterone synthesis during the SHRP led to alterations in anxiety-related behaviour and adrenocortical regulation later in development, with some behavioural effects being sex-dependent.