Abstract
Pregnancy and lactation are characterized by dramatic changes in the endocrine system and brain in mammalian females. These changes, with stress before pregnancy, are potential risk factors for the development of postpartum depression (PPD). A valid animal model of PPD is needed to understand the neurobiological basis of the depressive state of females. To explore a mouse model of PPD, we first assessed anxiety-like and depression-related behaviors in nulliparous (virgin), nonlactating primiparous, and lactating primiparous females in four inbred strains of mice (C57BL/6J, C57BL/6JJcl, BALB/cAnNCrlCrlj, and BALB/cAJcl). Pups from the nonlactating female group were removed one day after parturition to examine the effects of physical interaction with pups on the postpartum behaviors. Second, we investigated the additional effects of prepregnancy stress (restraint stress for 6 h/day for 21 days) on postpartum behaviors in the BALB/cAJcl strain. We found that females of the two BALB/c substrains showed decreased locomotor activity and increased anxiety-like and depression-related behaviors compared with females of the two C57BL/6 substrains. Behavioral differences were also observed between the two substrains of each strain. Additionally, pregnancy- and lactation-dependent behavioral differences were found in some strains: lactating BALB/cAJcl females traveled shorter distance than the females of the other reproductive state groups, while nonlactating and lactating BALB/cAJcl and C57BL/6J females showed increased depression-related behavior compared with nulliparous females. Lactating BALB/cAJcl and C57BL/6JJcl females exhibited decreased sucrose preference or anhedonia-like behavior compared with nulliparous and nonlactating females, although these results did not reach statistical significance after correction for multiple testing. An additional independent experiment replicated the marked behavioral changes in lactating BALB/cAJcl females. Moreover, increased anxiety-like behavior was observed in lactating BALB/cAJcl females that experienced prepregnancy stress. These results suggest genetic contributions to the regulation of anxiety-like and depression-related behaviors in female mice. Furthermore, this study suggests that pregnancy and lactation cause decreased locomotor activity and increased depression-related behaviors, which was consistently found in our results, and that prepregnancy stress enhances anxiety-like behavior in the BALB/cAJcl strain. The inbred strain of female mice may be used as a potential model of PPD to further study the genetic and neurobiological mechanisms underlying the development of this disorder.
Highlights
Pregnancy and lactation are characterized by significant changes in the endocrine system, brain, and behavior of females in mammals [1,2,3]
Significant strain differences were found in the distance traveled between BALB/c substrains; BALB/ cAJcl (CAJcl) females traveled longer distances than CACrlj females in each reproductive state group and in each 10min block
The decreased distance traveled in lactating CAJcl females and other behavioral results were replicated in another independent cohort of mice, as described in detail below
Summary
Pregnancy and lactation are characterized by significant changes in the endocrine system, brain, and behavior of females in mammals [1,2,3]. Becoming a mother is considered to be a significant experience accompanied by a positive mood, this life event has the potential to be physically and psychologically exhausting and distressing and could possibly be a risk factor for developing postpartum depression (PPD) [4]. The prevalence of PPD is estimated to be approximately 10–15%, depending on the criteria used for diagnosis [5,6,7]. Women with PPD often suffer from comorbid anxiety [9,10,11], and women with histories of prepartum depressive and anxiety symptoms are at increased risk for exacerbation or recurrence of the symptoms during the postpartum period [12,13,14]. Despite the high prevalence and negative outcomes, little is known regarding the etiology and pathophysiology of PPD; a useful animal model needs to be developed for elucidating the risk factors and neurobiological mechanisms underlying PPD
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