ARTICLES
Through undefined epigenetic processes, maternal effects influence
the development of defensive responses to threat in organisms rang-
ing from plants to mammals1,2.In the rat, such effects are mediated by
variations in maternal behavior, which serve as the basis for the trans-
mission of individual differences in stress responses from mother to
offspring3–5. Mother-pup contact in the rat primarily occurs within
the context of a nest-bout, which begins when the mother approaches
the litter, licks and grooms her pups, and nurses while occasionally
licking and grooming the pups6. There are stable individual differ-
ences in two forms of maternal behavior—LG and ABN—over the
first week of lactation6–10. Such naturally occurring variations in
maternal behavior are associated with the development of individual
differences in behavioral and HPA responses to stress in the offspring.
As adults, the offspring of ‘high-LG-ABN’ mothers are less fearful and
show more modest HPA responses to stress than the offspring of ‘low-
LG-ABN’ mothers6–9.Cross-fostering studies show that the biological
offspring of low-LG-ABN mothers reared by high-LG-ABN dams
resemble the normal offspring of high-LG-ABN mothers (and vice
versa9). These findings suggest that variations in maternal behavior
serve as a mechanism for the nongenomic transmission of individual
differences in stress reactivity across generations4,5,9. The critical
question concerns the mechanisms whereby these maternal effects, or
other forms of environmental ‘programming’, are sustained over the
lifespan of the animal.
Maternal behavior in the rat permanently alters the development of
HPA responses to stress through tissue-specific effects on gene
expression. The magnitude of the HPA response to acute stress is a
function of hypothalamic corticotropin-releasing factor (CRF)
release, which activates the pituitary-adrenal system. There are also
modulatory influences, such as glucocorticoid negative feedback that
inhibits CRF synthesis and release, thus dampening HPA