Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180 min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10 min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14 days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7 days, followed by measurement of intestinal permeability using the (51)CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability.
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