Early life stress effects on adult stress-induced corticosterone secretion and anxiety-like behavior in the C57BL/6 mouse are not as robust as initially thought.

Understanding environmental effects on mouse brain development would allow us to take advantage of powerful genetic tools to determine the interaction between genetic and epigenetic factors governing brain development in C57BL/6 mice. Experiment 1 examined whether time of day for neonatal manipulations affects adult stress-induced hormone secretion. Three rearing groups were examined: early handled (EH; dam removed 10 min/day); maternal separated (MS; dam removed 180 min/day); and an animal facility raised (AFR) control. Separations occurred during either the first or last 3 h of the light phase. Corticosterone (CORT) secretion in response to 100 dB white noise was assessed in adulthood. Both EH and MS males separated during the last 3 h of the light phase exhibited blunted stress-induced CORT compared to all other groups. Experiment 2 varied time of behavior testing. A fourth group was also added: maternal isolated (MI; separated from dam and littermates 180 min/day). Adult male behavior was assessed in three different tests. EH males tested in the elevated zero maze (EZM) during the light phase and MS males tested in the EZM during the dark phase exhibited diminished anxiety-like behavior compared to the other groups. We conclude that the EH protocol is marginally effective in blunting stress-induced CORT secretion and anxiety-like behavior in C57BL/6 mice, and these early handling effects are influenced by time of day. We also conclude that the 3 h MS or MI protocol is not effective in exacerbating future adult stress-induced CORT secretion or anxiety-like behavior in C57BL/6 mice.