PROGESTIN-ONLY CONTRACEPTIVE IMPLANT MODULATES BASELINE BEHAVIOR AND STRESS RESPONSE IN FEMALE MICE

Despite causing psychiatric side effects in some users, hormonal contraceptives (HC) are widely prescribed. The risk factors for their adverse effects remain elusive. Here, we aimed to characterize the risk group. We implanted a pellet releasing the synthetic progestin norethindrone into female C57BL/6J mice and studied the effects of HC on behavior and stress response. The mice underwent behavioral tests before and after a restraint stress paradigm to examine the effects of the HC implant on baseline and post-stress behavior. Using RFID chips, we tracked the mice in their home cage, providing information on their activity and sleep patterns. We found that the HC implant affected behavior in the home cage and in classic behavior testing. The activity in the home cage was drastically reduced by the HC treatment. While the placebo group showed an anxiety effect after stress, a smaller shift was observed in the HC group, reducing some baseline group differences. However, stress more strongly reduced home cage activity in HC-treated mice than in placebo-treated mice, with the HC group consistently being less active. To summarize, norethindrone has broad effects on behavior in female mice. It reduces the behavioral and physiological response to restraint stress, except for the home cage activity, which was more strongly affected by stress in the HC-treated mice. In follow-up experiments, we will investigate the molecular mechanisms underlying individual variability in behavior during HC treatment. The present study gives insights into the complex effects that HCs have on behavior, mental health, and stress response.