Developmental outcomes after gestational antidepressant treatment with sertraline and its discontinuation in an animal model of maternal depression

•Pre-conceptional maternal corticosterone and SSRI exposure impacted offspring outcome.•Pre-conceptional corticosterone altered stress response, anxiety and memory in females.•Male offspring exposed to sertraline during pregnancy were more active in the OFT.•Corticosterone and sertraline treatment interacted to impact OFT behavior in females.•Corticosterone or sertraline treatment did not impact FST behavior or neurogenesis. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to women before or during pregnancy to manage their depressive symptoms. However, there is still little knowledge regarding the long-term development effects of SSRI exposure for the fetus or the effects of discontinuing SSRI treatment during pregnancy. This study utilized a translational animal model of maternal depression (based on giving high levels of corticosterone (CORT, 40 mg/kg, s.c.) or vehicle (Oil) for 21 days prior to conception) to investigate the effects of sertraline (a frequently prescribed SSRI; 20 mg/kg p.o., treatment started ∼7 days prior to conception) and its discontinuation during pregnancy (on gestational day 16) compared to vehicle (water) treatment on the development of the offspring. Our results revealed that both corticosterone exposure prior to pregnancy and sertraline administration and its discontinuation during gestation had sex-specific effects on behavior in the adult offspring. In particular, pre-conceptional maternal corticosterone treatment impacted the stress response, anxiety-like behavior and cognitive performance in adult female offspring, while gestational SSRI exposure and its discontinuation compared to full-term exposure affected impulsivity in females, and exploratory behavior in males. More research is needed on the effects of exposure to antidepressant medication and its discontinuation compared to depression during pregnancy and how each impacts development to better help women make informed decisions about their medication use during pregnancy.