DO EARLY-LIFE EVENTS PERMANENTLY ALTER BEHAVIORAL AND HORMONAL RESPONSES TO STRESSORS

Early-life stimulation (e.g. brief handling) attenuates the behavioral and neuroendocrine responses to stressors encountered in adulthood, p articularly with respect to activation of hypothalamic-pituitary-adren al (HPA) activity. In contrast, if neonates were subjected to a more s evere stressor, such as protracted separation from the dam or exposure to an endotoxin, then the adult response to a stressor was exaggerate d. These early-life experiences program HPA functioning, including neg ative feedback derived from stimulation of hippocampal glucocorticoid receptors, and corticotropin-releasing hormone (CRH) and arginine vaso pressin (AVP) coexpression in PVN neurons, to modify the response to s ubsequent stressor experiences. The persistent variations of HPA activ ity observed in handled/stimulated animals may stem from alterations i n dam-pup interactions (e.g. increased arched-back feeding, licking, g rooming). In addition genetic makeup is critical in determining stress reactivity. For instance, BALB/cByJ mice are more reactive to stresso rs than C57BL/6ByJ mice, exhibiting greater HPA hormonal alterations a nd behavioral disturbances. BALB/cByJ also fail to acquire a spatial l earning response in a Morris water-maze paradigm, which has been shown to be correlated with hippocampal cell loss associated with aging. Ea rly-life handling of BALB/cByJ mice prevented these performance defici ts and attenuated the hypersecretion of ACTH and corticosterone elicit ed by stressors. The stressor reactivity may have been related to mate rnal and genetic factors. When BALB/cByJ mice were raised by a C57BL/6 ByJ dam, the excessive stress-elicited HPA activity was reduced, as we re the behavioral impairments. However, cross-fostering the more resil ient C57BL/6ByJ mice to a BALB/cByJ dam failed to elicit the behaviora l disturbances. It is suggested that genetic factors may influence dam -pup interactive styles and may thus proactively influence the respons e to subsequent stressors among vulnerable animals. In contrast, in re latively hardy animals the early-life manipulations may have less obvi ous effects. (C) 1998 ISDN. Published by Elsevier Science Ltd.