No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain

Abstract

The time around birth is accompanied by behavioural and physiological adaptations of the maternal brain, which ensure reproductive functions, maternal care and the survival of the offspring. In addition, profound neuroendocrine and neurobiological adaptations have been described with respect to behavioural and neuroendocrine stress responsiveness in rodents and human mothers. Thus, the hormonal response of the hypothalamo-pituitary-adrenal (HPA) axis and the response of the sympathetic nervous system to emotional and physical stressors are severely attenuated. Moreover, anxiety-related behaviour and emotional responsiveness to stressful stimuli are reduced with the result of general calmness. These complex adaptations of the maternal brain are likely to be a consequence of an increased activity of brain systems with inhibitory effects on the HPA axis (such as the oxytocin and prolactin systems) and of a reduced activity of excitatory pathways (noradrenaline (norepinephrine), corticotrophin-releasing factor and opioids). Experimental manipulation of these systems using complementary approaches indeed demonstrates their importance in these maternal brain adaptations. Maternal stress adaptations are not only important for the healthy prenatal development of the offspring by preventing excessive glucocorticoid responses and in the promotion of postnatal maternal behaviour, but are also vital for the well-being of the mother and her mental health.

Figure 1. Schematic representation of some of the neuroendocrine alterations that occur between virgin and lactating dams

Virgins are characterized by having higher levels of opioid and noradrenergic (NA) inputs to the PVN than in lactating animals but lower expression of oxytocin (OXT) and prolactin (PRL). Whereas opioids have no apparent influence on OXT in virgin animals, they have been shown to increase OXT in the PVN during lactation. Furthermore, the effect of endogenous opioids on CRF release is attenuated during lactation. The combined effect of these alterations is an enhanced corticotrophin-releasing factor (CRF) release in response to stress in virgins, which leads to the release of corticotrophin (ACTH) and increased anxiety- and depression-related behaviour in comparison to lactating animals. By contrast, the low OXT and PRL levels, as well as elevated the CRF level, leads to lower levels of maternal behaviour in virgins compared with lactating animals. Thus disruption of these factors may contribute to postpartum depression, which is associated with increased anxiety and depression, as well as reduced maternal care. Black and thick arrows represent the predominant pathways in virgins and lactating animals while the grey and thin arrows show the systems that are at low levels (i.e. OXT and PRL in virgins) or attenuated (i.e. opioid and NA in lactation). Blocked lines represent factors which are inhibitory; factors with thick and black lines again represent the predominant systems in virgins or lactating animals compared with one another.