title: Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation.
abstract: The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence has cast doubt on the effectiveness of SSRIs, these results support their therapeutic use in the treatment of PPD.
authors.affiliation: Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Jury
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America.
authors.forename: Betsy A
authors.initials: BA
authors.lastname: McCormick
authors.affiliation: Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America; Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America.
authors.forename: Nelson D
authors.initials: ND
authors.lastname: Horseman
authors.affiliation: Department of Psychiatry, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Benoit
authors.affiliation: Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America; Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America; Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, Ohio, 45267, United States of America.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gregerson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001942:Breast Feeding; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D019052:Depression, Postpartum / Q000188:drug therapy; D065847:Dorsal Raphe Nucleus / Q000378:metabolism / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007774:Lactation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors