Zarcaly Quintero Martinez¹, Amanda Lopez Ramirez¹, Xaymarie Serrano Velazquez¹, Christian Bravo Rivera¹, Orlando Torres Rodriguez^1
1Depts. of Psychiatry and Anatomy & Neurobiology, University of Puerto Rico School of Medicine, San Juan, PR 00936

INTRODUCTION: The manifestation of anxiety differs between men and women, with women having higher diagnosis rates and experiencing a greater burden of illness (McLean et al., 2011). Additionally, anxiolytic medications have varying effects on men and women (Heyden et al., 2009). However, it remains unclear whether anxiolytics affect higher cognitive functions, such as cost-benefit decision-making, differently in men and women.

METHODS: Therefore, we investigated the impact of commonly prescribed anxiolytics, propranolol, and paroxetine, on approach/avoidance conflict behaviors using the platform-mediated avoidance (PMA) task in male and female mice. In the PMA task, thirsty, freely behaving mice choose between seeking a light-signaled water reward or avoiding a tone-signaled electrical foot shock by stepping onto a safety platform far from the reward port.

RESULTS: After comprehensive PMA training, females exhibited balanced approach/avoidance behaviors, whereas males showed excessive approach behaviors. Both propranolol (10 mg/kg, i.p.) and paroxetine (10 mg/kg, i.p.) increased avoidance behavior during conflict (p < 0.044). Upon closer examination, propranolol-treated males displayed balanced approach/avoidance behavior, while females exhibited excessive avoidance during conflict. These effects were specific to conflict situations, as propranolol had no impact on approach/avoidance behaviors in non-conflict PMA conditions (p > 0.17). Paroxetine treatment increased excessive avoidance in both males and females (p < 0.034), and this effect was not dependent on conflict, as we observed the same effect in non-conflict PMA conditions (p = 0.0024).

CONCLUSION: In summary, our study revealed that propranolol and paroxetine induced maladaptive avoidance behavior in females, while propranolol, but not paroxetine, promoted adaptive and balanced approach/avoidance behaviors during conflict. Future research should further investigate how anxiolytics interact with cost-benefit decision-making in both men and women.

IACUC APPROVAL NUMBER: A700222

ACKNOWLEDGMENTS: Supported by NIH grants MH123495 and MH052223 to CB-R, MH108924, and MH101214 to BL. Special thanks to the BLISP fellows’ class of summer 2023.