The critical question concerns the potential consequences of these differences in maternal behavior for the development of behavioral and neuroendocrine responses to stress. As adults, the offspring of high-LG mothers show reduced plasma ACTH and corticosterone responses to acute stress by comparison to the adult offspring of lowLG mothers.39,67 Circulating glucocorticoids act at GR sites in corticolimbic structures, such as the hippocampus, to regulate HPA activity. Such negative-feedback effects commonly target CRF synthesis and release at the level of the PVNh. Enhanced GR activation in the hippocampus is associated with decreased hypothalamic CRF levels. The high-LG offspring showed significantly increased hippocampal GR mRNA expression, enhanced glucocorticoid negative-feedback sensitivity, and decreased hypothalamic CRF mRNA levels.39 Moreover, the magnitude of the corticosterone response to acute stress was significantly correlated with the frequency of both maternal LG (r=-0.61) during the first week of life, as was the level of hippocampal GR mRNA and hypothalamic CRF mRNA expression (all r values >0.70).39
