Stress during gestation induces lasting effects on emotional reactivity of the dam rat

Abstract

Human and animal studies indicate that repeated stress during pregnancy can produce long-term biological and behavioural disorders in the offspring. In contrast, although maternal stress is supposed to induce an increase of maternal anxiety, few studies have been conducted to demonstrate it. Therefore, in the present study we examined the emotional reactivity in stressed (chronic restraint stress applied 3× 45 min per day during the last week of pregnancy) and unstressed females rats after the weaning of their pups. Restraint stress procedure reduced the body weight gain both during pregnancy and up to four weeks after the stress period. Stressed dams presented a reduction of exploration and of corticosterone levels when exposed to a novel environment (25 and 49 days post-stress). They spent less time in the open arms of the elevated plus-maze (26 days post-stress). Finally, they showed no increase in the time spent in immobility after a second exposure to the forced-swim test (35–36 days post-stress). In the contrary, such differences were not observed when the chronic stress procedure was applied on virgin females. Overall, our results show that, chronic stress during gestation induces lasting effects on emotional reactivity of the dams, thus indicating that gestation constitutes a critical period in the vulnerability to stressful events also for the mother.

Introduction

Stressful events such as pregnancy, labour and lactation occur simultaneously with marked fluctuations in plasma levels of steroid hormones, known to be involved in the vulnerability to emotional disorders. The first days postpartum are often associated with the onset of major emotional vulnerability. However, pregnancy and lactation are generally described as hyporesponsive periods to stress [15], [34], [53]. Thus, it remains unclear if pregnancy constitutes a critical period involved in the vulnerability to stress. In rats, chronic maternal stress during pregnancy has been used to study the impact of early stress on development and later vulnerability to stress in offspring. Several paradigms of stress including daily subcutaneous injection [8], water immersion [9], overcrowding [14] or restraint stress [24], [49] induce long-term behavioural [7], [17], [48], [55] and neurobiological [19], [24], [28] abnormalities in the offspring. Processes mediating the effect of prenatal stress on the offspring have been proposed to involve both prenatal [3] and postnatal [38], [42] maternal factors.

While the impact of maternal stress during pregnancy on physiology and behaviour of the offspring has been well documented (for review, see [23], [50]), up to date few studies have explored the effect of gestation stress on the maternal behaviour [25], [29], [35], [36] and none on the behaviour of the dams after weaning. Measurement of maternal anxiety during lactation is difficult to validate since it involves the reactivity to pup’s separation [43]. In the present study, we evaluate reactivity of stress in several paradigms, 1–5 weeks after the weaning of the pups. Our results demonstrate that stress during pregnancy durably decreases maternal body weight growth, increases anxiety-like behaviour and affects reactivity to stress in primiparous females more than one month after the stress procedure. Finally, in another experiment we show that chronic stress has no effect on virgin females suggesting that gestational state is a period of particular vulnerability to stress.