Endocrine Abstracts (2009) 20 S6.3

Programming of the stress system by the maternal care in animal models

S Maccari, S Morley-Fletcher & M Darnaudery

University of Lille, Lille, France.

Life events occurring during the perinatal period have strong permanent long-term effects on the behavioural and neuroendocrine response to stressors. In rats, repeated restraint stress of the pregnant dam during the last week of pregnancy produces long lasting changes in the HPA axis function and behaviours in the offspring. These changes include a hyperactivity of HPA axis response associated with a reduction in the number of hippocampal corticosteroid receptors. The HPA dysfunctions have been reported in infant, young adult and aged animals, therefore suggesting a permanent effect of early stress. Interestingly, after the confrontation to an intense inescapable footshock, prenatal restraint stress (PRS) rats durably show a blunted corticosterone secretion after stress. PRS also induces a hyporeponse of the HPA axis when animals are exposed to an alcohol challenge. Rats exposed to a PRS also show behavioural disturbances known to be related to the HPA axis. Indeed, PRS produces high anxiety levels and depressive-like behaviour during adulthood including sleep disorders related to depression. With ageing, these animals exhibit memory impairments in hippocampo-dependent tasks. Despite the permanent imprinting induced by stress in utero, the dysfunctions observed after PRS can be reversed by environmental or pharmacological strategy. For example, early adoption or environmental enrichment during adolescence, as well as a chronic treatment with Insulin-like growth factor 1 in aged animals attenuated some HPA dysfunction’s produced by PRS. Mechanisms underlying the PRS effects on the offspring remain largely unknown. However, previous works demonstrated that maternal glucocorticoids during pregnancy may play an important role in the HPA disturbances reported. Thus, stressed mothers show high glucocorticoid levels during pregnancy. Furthermore, in the offspring of stressed mothers, the HPA response to stress is normalised by maternal adrenalectomy during pregnancy. Recently, our group has reported that repeated restraint stress during pregnancy leads to a decrease of the placental 11β-HSD2 activity. Finally, gestational stress has long lasting effects on HPA axis and behaviour in female dams. Thus, during lactating period, stressed mothers show an impairment of maternal care and low aggressive behaviour against a male intruder. Moreover, females stressed during pregnancy show an increase of anxiety-like behaviour several weeks after the end of the stress period. Given that, several evidences suggest that changes in maternal care may durably program offspring’s HPA function and behaviours, it could be postulated that the alterations of the maternal behaviour during the early postnatal period may also strongly contribute to the long-term effect described after prenatal stress.

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