THU403 Fluoxetine Administration During The Peripartal Period And The Effect On Calcium Metabolism And Serotonin Signaling In The Mammary Gland

Abstract

Abstract Disclosure: H. Fricke: None. C.J. Krajco: None. M.J. Perry: None. L.L. Hernandez: None. Postpartum depression affects an estimated 10 to 15% of the population. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants during pregnancy and lactation and are considered safe to use during pregnancy and lactation. During lactation, bone resorption is increased to mobilize calcium via a serotonin-dependent hormonal cascade. In the mammary gland, serotonin acts via the Hedgehog (Hh) signaling pathway to liberate calcium from bone for milk. Previously, our lab has determined that a high dose of the SSRI fluoxetine (FLX) during the peripartal period impacts calcium and serotonin metabolism during lactation. We hypothesize that a low dose of FLX during the peripartal period will upregulate Hh signaling and subsequently modulate calcium and serotonin metabolism during lactation, and that this impact will vary depending on whether FLX was administered during lactation only or throughout gestation and lactation. Female C57BL/6J mice were randomized to receive FLX (2 mg/kg) or saline daily via i.p. injection from parturition to the end of lactation (D21; lactation only), or from P0 to D21 (gestation + lactation), creating the following treatments: lactation saline (LS; n=10), lactation FLX (n=16), gestation + lactation saline (G+LS; n=5), and gestation + lactation FLX (G+LF; n=15). Circulating serotonin and calcium levels were measured in the serum at P0, the beginning of lactation (D2), and D21, and mammary glands were harvested at D21 for gene expression analysis. When normalized to P0 measurements, there were no differences in circulating calcium or serotonin levels between control and FLX groups at D2 or D21 when treated during lactation only, or gestation and lactation. However, G+LF mice tended to have a lower circulating serotonin level than G+LS mice on D21 (p=0.0770). At D21, gene expression of glioblastoma transcription factor 1 (GLI1) and sonic hedgehog (SHH), both members of the Hh signaling pathway, were altered in the G+LF group. There was a tendency for GLI1 expression to be increased in the G+LF dams (p=0.0634) and SHH was significantly increased in the G+LF dams (p=0.0382) when compared to the G+LS dams. These data suggest that a low dose of FLX during lactation only may not have a significant impact on calcium and serotonin metabolism via alterations in Hh signaling in the mammary gland but may be impacted when administered throughout the entire peripartal period. Presentation: Thursday, June 15, 2023