C. Caldji et al., MATERNAL-CARE DURING INFANCY REGULATES THE DEVELOPMENT OF NEURAL SYSTEMS MEDIATING THE EXPRESSION OF FEARFULNESS IN THE RAT, Proceedings of the National Academy of Sciences of the United Statesof America, 95(9), 1998, pp. 5335-5340
The mothers of infant rats show individual differences in the frequenc
y of licking/grooming and arched-back nursing (LG-ABN) of pups that co
ntribute to the development of individual differences in behavioral re
sponses to stress. As adults, the offspring of mothers that exhibited
high levels of LG-ABN showed substantially reduced behavioral fearfuln
ess in response to novelty compared with the offspring of low LG-ABN m
others. In addition, the adult offspring of the high LG-ABN mothers sh
owed significantly (i) increased central benzodiazepine receptor densi
ty in the central, lateral, and basolateral nuclei of the amygdala as
well as in the locus ceruleus, (ii) increased alpha(2) adrenoreceptor
density in the locus ceruleus, and (iii) decreased corticotropin-relea
sing hormone (CRH) receptor density in the locus ceruleus, The express
ion of fear and anxiety is regulated by a neural circuitry that includ
es the activation of ascending noradrenergic projections from the locu
s ceruleus to the forebrain structures. Considering the importance of
the amygdala, notably the anxiogenic influence of CRH projections from
the amygdala to the locus ceruleus, as well as the anxiolytic actions
of benzodiazepines, for the expression of behavioral responses to str
ess, these findings suggest that maternal care during infancy serves t
o ''program'' behavioral responses to stress in the offspring by alter
ing the development of the neural systems that mediate fearfulness.