Early weaning impairs fear extinction and decreases brain-derived neurotrophic factor expression in the prefrontal cortex of adult male C57BL/6 mice.

We examined the developmental effects of early weaning on anxiety and the extinction of fear memory in male C57BL/6 mice. Early weaning led to increased freezing behaviors after fear conditioning via the foot-shock method both during extinction training and in a test of extinction recall, but did not induce significant changes in anxiety-like behavior. In addition, we found that the levels of brain-derived neurotrophic factor (BDNF) protein and mRNA transcripts for BDNF exon III in the medial prefrontal cortex (mPFC) at the time of extinction recall were impaired in early-weaned mice compared to normally weaned mice. In light of consistent finding that early-weaned mice experience greater stress at weaning, these data suggest that early weaning of male C57BL/6 mice is valuable for studies of the pathogenesis of post-traumatic stress disorder.