The study investigated whether transient pharmacological inhibition of aldosterone synthesis during the early postnatal stress‑hyporesponsive period (SHRP) affects later behaviour and adrenocortical stress responsiveness, and whether such effects differ between males and females. The SHRP is a developmental window when hypothalamic–pituitary–adrenal (HPA) axis reactivity is normally low; perturbations during this period may have lasting consequences. The authors tested these questions using the aldosterone synthase inhibitor FAD286 administered to neonatal rats.
Newborn Wistar rat pups (males n=40, females n=40) received oral FAD286 at 30 mg/kg per day or vehicle from postnatal day (PND) 3 to PND9. To confirm pharmacodynamic effects, serum and adrenal glands from a subset of 10‑day‑old pups were analysed. The remaining animals were weaned on PND21.
Behavioural testing proceeded as follows: general locomotor activity was assessed in the open‑field on PND23, anxiety‑related behaviour was assessed in the elevated plus‑maze on PND29, and salt‑preference testing was performed (age for salt test not specified in the abstract). At PND46, half of each treatment/sex group were exposed to restraint stress for 120 minutes to assess adrenocortical stress responsiveness in adolescence. The source abstract reports group sizes, dosing regimen, time points, and the main assays but does not provide detailed procedural parameters, full methodological controls, or statistical methods in the abstract.
Analysis at PND10 demonstrated that neonatal treatment with FAD286 affected adrenal gene expression and circulating steroid levels. Specifically, FAD286 treatment resulted in increased adrenal expression of CYP11B2 (aldosterone synthase) and CYP11B1 (11β‑hydroxylase). Serum steroid measures showed increased corticosterone concentrations and decreased serum aldosterone concentrations in 10‑day‑old pups, consistent with effective pharmacological inhibition of aldosterone synthesis and compensatory changes at the level of steroidogenic gene expression.
The study reported that FAD286 did not alter general locomotor activity assessed in juvenile rats in the open‑field test (PND23). Anxiety‑related behaviour assessed later (elevated plus‑maze on PND29) was altered after neonatal FAD286 treatment, with the pattern of change differing by sex. Salt‑preference testing was performed, but the abstract does not provide details of findings from that test beyond the timeline.
During adolescence, animals that had received early FAD286 showed an overall increase in aldosterone concentrations versus controls; however, the aldosterone response to restraint stress was not altered by early treatment. Basal corticosterone concentrations in adolescence were reported as unchanged, whereas the corticosterone response to the 120‑minute restraint stress was enhanced in animals exposed to neonatal FAD286.
A key behavioural finding was that postnatal inhibition of aldosterone synthase produced increased anxiety‑like behaviour in female rats but not in male rats. The abstract states that some behavioural effects were sex‑dependent, with the most clear example being heightened anxiety‑like behaviour in females following neonatal FAD286. The source does not provide the detailed behavioural metrics, effect sizes, or statistical comparisons in the abstract.
Transient pharmacological blockade of aldosterone synthesis during the SHRP produced persistent alterations in both anxiety‑related behaviour and adrenocortical regulation later in development. The data reported in the abstract indicate compensatory changes in adrenal steroidogenic gene expression in neonates, reduced aldosterone and increased corticosterone at PND10, and later increases in adolescent aldosterone along with an enhanced corticosterone response to restraint. Behavioural consequences included sex‑specific increases in anxiety‑like behaviour (females). These outcomes suggest that early disruption of aldosterone synthesis can produce long‑term changes in neuroendocrine regulation and behaviour.
This summary is based on the article abstract and metadata. The source is a preprint and has not been peer reviewed. The abstract provides key findings, dosing, sample sizes, and time points but does not report detailed numerical results, statistical analyses, full methods, or effect sizes; those details are not reported in the abstract and would require consultation of the full manuscript. The abstract also does not report exact ages or conditions for some tests (for example, the timing/results of salt‑preference testing) or sex‑stratified hormone data beyond the statements summarized above.
Funding and disclosures: The authors reported support from the European Union (grant information provided in the source). The authors declared no competing interests. The manuscript is posted on bioRxiv and has not been certified by peer review.