Naturalistic rodent models of chronic early-life stress

Dev Psychobiol. 2014 Dec;56(8):1675-88. doi: 10.1002/dev.21230. Epub 2014 Jun 9.


A close association between early-life experience and cognitive and emotional outcomes is found in humans. In experimental models, early-life experience can directly influence a number of brain functions long-term. Specifically, and often in concert with genetic background, experience regulates structural and functional maturation of brain circuits and alters individual neuronal function via large-scale changes in gene expression. Because adverse experience during sensitive developmental periods is often associated with neuropsychiatric disease, there is an impetus to create realistic models of distinct early-life experiences. These can then be used to study causality between early-life experiential factors and cognitive and emotional outcomes, and to probe the underlying mechanisms. Although chronic early-life stress has been linked to the emergence of emotional and cognitive disorders later in life, most commonly used rodent models of involve daily maternal separation and hence intermittent early-life stress. We describe here a naturalistic and robust chronic early-life stress model that potently influences cognitive and emotional outcomes. Mice and rats undergoing this stress develop structural and functional deficits in a number of limbic-cortical circuits. Whereas overt pathological memory impairments appear during adulthood, emotional and cognitive vulnerabilities emerge already during adolescence. This naturalistic paradigm, widely adopted around the world, significantly enriches the repertoire of experimental tools available for the study of normal brain maturation and of cognitive and stress-related disorders including depression, autism, post-traumatic stress disorder, and dementia.

Keywords: animal models; dementia; depression; early-life experience; fragmentation; hippocampus; maternal care; memory; post-traumatic stress disorder; stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Animals, Newborn* / growth & development
  • Animals, Newborn* / metabolism
  • Animals, Newborn* / physiology
  • Brain* / growth & development
  • Brain* / metabolism
  • Brain* / physiopathology
  • Disease Models, Animal*
  • Mice
  • Rats
  • Stress, Psychological* / complications
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / physiopathology