Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation.

Nicholas J Jury,Nelson D Horseman,Stephen C Benoit,Betsy A Mccormick,Karen A Gregerson,Jodi Pawluski

doi:10.1371/journal.pone.0117339

Nicholas J Jury, Nelson D Horseman + Show 4 more

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https://doi.org/10.1371/journal.pone.0117339

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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.

Highlights

Mood alterations during the postpartum and postpartum depression (PPD) adversely affect the mother, and disrupt bonding and the health of the child [1]
We examined the effect (s) of sub-chronic SSRI treatment on affective state, as measured by depression-related and anxiety-related behaviors in the postpartum
Our experiments were conducted in C57BL/6J mice, whereas, the aforementioned studies were conducted in Sprague-Dawley Rats, which could account for the different results

Summary

Introduction

Mood alterations during the postpartum and postpartum depression (PPD) adversely affect the mother, and disrupt bonding and the health of the child [1]. PPD (defined in the psychiatric nomenclature as a major depressive disorder with a specifier of onset during pregnancy and/or following childbirth) affects 10–20% of women who give birth [5,6,7,8]. It is an evolutionary imperative that female mammals cope with the physiological stresses of pregnancy, child birth, and lactation without suffering the debilitations inherent with PPD. From this biological perspective, attention naturally focuses on PPD as a disorder, and several studies have suggested specific mechanisms of PPD [9;10,11]. SSRIs are the first line of pharmacotherapy in PPD and relieve depressive symptoms in most of these patients [4,20]

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