Bacterial infection early in life protects against stressor-induced depressive-like symptoms in adult rats

Staci D. Bilbo*, Raz Yirmiya, Jose Amat, Evan D. Paul, Linda R. Watkins, Steven F. Maier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Both early-life stress and immune system activation in adulthood have been linked independently to depression in a number of studies. However, the relationship between early-life infection, which may be considered a "stressor", and later-life depression has not been explored. We have reported that neonatal bacterial infection in rats leads to exaggerated brain cytokine production, as well as memory impairments, to a subsequent peripheral immune challenge in adulthood, and therefore predicted that stressor-induced depressive-like symptoms would be more severe in these rats as well. Rats treated on postnatal day 4 with PBS or Escherichia coli were as adults exposed to inescapable tailshock stress (IS), and then tested for sucrose preference, social exploration with a juvenile, and overall activity, 1, 3, 5, and 7 days following the stressor. Serum corticosterone and extracellular 5-HT within the basolateral amygdala were measured in a second group of rats in response to the IS. IS resulted in profound depressive-like behaviors in adult rats, but, surprisingly, rats that suffered a bacterial infection early in life had blunted corticosterone responses to the stressor and were remarkably protected from the depressive symptoms compared to controls. These data suggest that early-life infection should be considered within a cost/benefit perspective, in which outcomes in adulthood may be differentially protected or impaired. These data also suggest that the immune system likely plays a previously unsuspected role in "homeostatic" HPA programming and brain development, which may ultimately lend insight into the often-contradictory literature on cytokines, inflammation, and depression.

Original languageAmerican English
Pages (from-to)261-269
Number of pages9
Issue number3
StatePublished - Apr 2008

Bibliographical note

Funding Information:
The authors thank Alexis Northcutt for technical assistance. This work was supported in part by NIMH Grant MH076320.


  • Corticosterone
  • Cytokines
  • Depression
  • Postnatal
  • Social exploration
  • Sucrose preference


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