Early Postnatal Androgenic Activity Inhibition Produces Differential Long‐Term Alterations in Anxiety‐Like Behavior in Young Adult Male and Female Wistar Rats

Sex differences in anxiety-like behavior are influenced by gonadal steroids, yet the contribution of early postnatal androgen signaling and testosterone metabolic pathways to the long-term organization of these behaviors remains unclear. Wistar male and female rats received daily s.c. injections from postnatal day (P) 1 to P5 of vehicle, flutamide, letrozole, or finasteride. In young adult animals, locomotor activity and anxiety-like behavior were evaluated via the open field test (OFT) and elevated plus maze (EPM). Females showed higher locomotor activity than males in both tests. Control females showed a less anxiety-like profile than control males in the EPM. Flutamide treatment abolished sex differences in EPM open-arm anxiety-related measures and increased the number of freezing episodes and their duration in the OFT. However, finasteride treatment preserved the sex differences observed in the control groups in anxiety-like measures. Finally, aromatase inhibition abolished sex differences in anxiety-like behavior and induced an anxiolytic-like effect in males, as indicated by increased open-arm entries relative to control males. These findings indicate that androgen-related pathways during early postnatal life shape adult anxiety-like behavior in a sex-dependent and pathway-dependent manner and highlight aromatization as a key mechanism in the organization of EPM behavioral outcomes in males.