The effect of adverse rearing environments on persistent memories in young rats: removing the brakes on infant fear memories

Mental health problems are often assumed to have their roots in early-life experiences. However, memories acquired in infancy are rapidly forgotten in nearly all species (including humans). As yet, a testable mechanism on how early-life experiences have a lasting impact on mental health is lacking. In these experiments, we tested the idea that infant adversity leads to an early transition into adult-like fear retention, allowing infant memories to have a longer-lasting influence. Rats were exposed to maternal separation (3 h per day) across postnatal days (P) 2-14, or their mother was given corticosterone in her drinking water across the same period. Infant rats were then trained to fear a conditioned stimulus (CS) paired with an aversive unconditioned stimulus (US) on P17. Retention of the fear association was then tested 1-55 days later. When tested one day after the CS-US association was formed, both standard-reared (SR) and maternally-separated (MS) rats exhibited strong memory. However, when tested 10 days later, SR rats exhibited robust forgetting, whereas MS rats exhibited near-perfect retention. These effects were mimicked by exposing the mother to the stress hormone corticosterone in the drinking water. Finally, fear associations in P17 MS rats were retained for up to 30 days. Our findings point to differences in retention of fear as one factor that might underlie the propensity of stress-exposed individuals to exhibit early anxiety symptoms and suggest that manipulations of the corticosterone system may hold the key to ameliorating some of the effects of early stress on persistent retention of fear. Translational Psychiatry (2012) 2, e138; doi:10.1038/tp.2012.65; published online 10 July 2012