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Administration of Fluoxetine or a Small Molecule TPH1 Inhibitor Affects Litter Size, Pup Mortality, and Milk Yield During Murine Pregnancy and Lactation
Author(s) -
Weaver Samantha,
Fricke Hannah,
Hernandez Laura
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.457.5
Subject(s) - lactation , endocrinology , medicine , litter , serotonin reuptake inhibitor , serotonin , fluoxetine , saline , weight gain , biology , pregnancy , genetics , receptor , agronomy , body weight
Non‐neuronal serotonin regulates milk synthesis in an autocrine‐paracrine manner during lactation. Selective Serotonin Reuptake Inhibitors (SSRI), including Fluoxetine, are the most commonly prescribed antidepressants during pregnancy and lactation in the United States. SSRI increase local activity of serotonin in both neuronal and non‐neuronal tissues, including the mammary gland. The objective of this study was to examine the effects of SSRI administration during lactation on milk yield, pup weight, pup mortality, and litter size. As a negative control, we used a small‐molecule inhibitor of the rate‐limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Beginning the day after pregnancy (d1 after cervical plug), C57Bl/6J dams were administered 20 mg/kg of either saline or fluoxetine daily via intraperitoneal injection through d21 of lactation. Additionally, on d1 of pregnancy, dams were either maintained on a control diet or loaded on a control diet fortified with a small‐molecule inhibitor of Tph1. There were three treatment groups: injected with saline and receiving control chow (CON; n =15), fluoxetine/control chow (FLX; n =11), saline/Tph1 inhibitor chow (TPH1; n =14). Litter size on d0 was recorded, as was pup mortality throughout lactation. Milk yield per pup was determined using the weigh‐suckle‐weigh method and pup weight gain was recorded. Of all dams enrolled in the study (19 CON, 34 FLX, 26 TPH1), a certain proportion were excluded because all pups were found dead. By treatment, 21.1% (4/19) of CON dams, 67.6% (23/34) of FLX dams, and 46.2% (12/26) of TPH1 dams were excluded due to a dead/killed litter. Of those dams that kept all pups, FLX dams had smaller litters ( P =0.01; 6.5 ± 0.4 vs. 4.6 ± 0.5 vs. 6.4 ± 0.5 pups for CON, FLX, and TPH1) and tended to have more dead pups ( P =0.06; 0.7 ± 0.2 vs. 0.9 ± 0.3 vs. 0.2 ± 0.1 dead pups for CON, FLX, and TPH1) than CON or TPH1 dams. FLX dams also produced less milk ( P =0.03) than TPH1 or CON dams and subsequently had pups that gained less weight throughout lactation ( P <0.0001; 4.9 ± 0.5 vs. 4.4 ± 0.5 vs. 4.7 ± 0.5 g/pup for CON, FLX, and TPH1). Collectively, this data suggests that FLX administration throughout pregnancy and lactation may have adverse effects on pup development both in utero and during lactation. While previous literature has established that SSRI are the safest antidepressants due to minimal side effects, our data suggests that FLX treatment affects the dam's gestational and lactational capacity and therefore pup growth during pregnancy and lactation. Support or Funding Information Karos Pharmaceuticals National Science Foundation Graduate Research Fellowship Grant No. DGE‐1256259