Anxiety behaviour of the male rat on the elevated plus maze: associated regional increase in c-fos mRNA expression and modulation by early maternal separation.

Stressful stimuli cause region-specific increases in c-fos expression within the rat brain. Early maternal separation (EMS) is a model of early life adversity that results in long lasting changes to stress and anxiety responses. This study examined the regional distribution of c-fos mRNA after exposure to the elevated plus-maze (EPM) and how EMS altered this pattern. On each of post-natal days 5-21 pups were separated from the dam for 6 h -- control rats remained undisturbed. At 70 days old, male offspring were either exposed to the EPM or left undisturbed in the home cage. After exposure to the EPM, c-fos mRNA expression was significantly increased in specific brain areas, including cingulate cortex, medial amygdala and hippocampus. EMS rats displayed greater anxiety behaviour on the EPM vs. controls. Although EMS caused no overall effect on basal c-fos mRNA, a significant interaction between treatment group and exposure to the EPM occurred in the dentate gyrus and piriform cortex, with lower EPM-induced mRNA levels in EMS rats. The region-specific increase in c-fos mRNA reflects activation of neural circuits associated with EPM-induced anxiety. The effect of EMS on this activation in the two regions suggests these areas may contribute to the differential response to the anxiogenic stress of the EPM.