Differences in stress-induced changes in extinction and prefrontal plasticity in postweanling and adult animals.

BACKGROUND Postweaning is a critical developmental stage during which the medial prefrontal cortex (mPFC) undergoes major changes and the brain is vulnerable to the effects of stress. Surprisingly, the engagement of the mPFC in extinction of fear was reported to be identical in postweanling (PW) and adult animals. Here, we examined whether the effect of stress on extinction and mPFC plasticity would be similar in PW and adult animals. METHODS PW and adult animals were fear conditioned and exposed to the elevated platform stress paradigm, and extinction and long-term potentiation were examined. The dependency of stress-induced modulation of extinction and plasticity on N-methyl-D-aspartate receptors was examined as well. RESULTS We show that exposure to stress is associated with reduction of fear and enhanced induction of long-term potentiation (LTP) in PW pups, in contrast to its effects in adult animals. Furthermore, we report opposite effects in the occlusion of LTP following the enhanced or impaired extinction in the two age groups and that the reversal of the effects of stress is independent of N-methyl-D-aspartate receptor activation in PW animals. CONCLUSIONS Our results show that qualitatively different mechanisms control the modulatory effects of stress on extinction and plasticity in postweanling pups compared with adult rats. Our results point to significant differences between young and adult brains, which may have potential implications for the treatment of anxiety and stress disorders across development.