Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat

Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat

^*Developmental Neuroendocrinology Laboratory, Douglas Hospital Research Centre, Departments of Psychiatry, and Neurology and Neurosurgery, McGill University, Montreal, Canada, H4H 1R3; and ^†Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322

Communicated by Bruce S. McEwen, The Rockefeller University, New York, NY (received for review August 31, 1997)

Abstract

The mothers of infant rats show individual differences in the frequency of licking/grooming and arched-back nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased α₂ adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus 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 stress, these findings suggest that maternal care during infancy serves to “program” behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Developmental Neuroendocrinology Lab., Douglas Hospital Research Centre, 6875 Boul. LaSalle, Montreal, Quebec H4H 1R3, Canada. e-mail: mdmm{at}musica.mcgill.ca
ABBREVIATIONS:

HPA,

hypothalamic–pituitary–adrenal;

CRH,

corticotropin-releasing hormone;

oCRH,

ovine CRH;

BZ,

benzodiazepine;

CBZ,

central BZ;

H,

handled;

NH,

nonhandled;

LG-ABN,

licking/grooming–arched-back nursing;

CnA,

central nucleus of the amygdala