Sexually dimorphic and time-dependent influence of active avoidance learning by vilazodone in C57BL/6J mice

The effects of vilazodone (VZD) on the acquisition of active avoidance behavior were examined in C57BL/6J mice. Both female and male mice were assigned to three groups (n = 8 per group per sex): the vehicle control group (VEH), the 0.5 mg kg^-1 vilazodone lower dose group (VZD0.5) and the 1 mg kg^-1 vilazodone higher dose group (VZD1.0). Spontaneous locomotion and anxiety-like behaviour were assessed after drug administration intraperitoneally in an open field test (OFT). Another cohort of mice was trained in a three-day shuttle box active avoidance test (AAT) after drug administrations with the aim of evaluating the effects of VZD on the acquisition of active avoidance behaviour. In the OFT, VZD decreased freezing time in the corner area in both female and male mice, indicating reduced anxiety-like behaviours. In the AAT, the active avoidance rate was significantly improved on day 1 in female mice and day 2 in male mice, suggesting that VZD facilitated active avoidance learning with sexual dimorphism. Furthermore, the increased active avoidance rates were negatively correlated with freezing time during training. Interestingly, these group differences and correlations diminished on day 3, implying that the facilitation was restricted to early training phases. Collectively, VZD facilitates the acquisition of active avoidance behaviour in mice with distinct sexual dimorphism and temporal dynamics.