Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus

Children that are abused have an increased risk for developing psychiatric disorders later in life, because of the negative effects of stress on the developing brain. We used a maternal separation model in rats to see how neurotrophins, stress hormones, behavior and the anti-oxidant potential of serum are affected. Rat pups were separated from their mothers for 3 h/day on days 2-14. Maternal separation caused changes in levels of NGF and NT-3 in the dorsal and ventral hippocampus, increased basal corticosterone levels and decreased ACTH levels after acute restraint stress. The anti-oxidant potential of the rat serum was significantly lower in the maternal separation group. Depressive-like behavior, measured during a forced swim test, was seen in maternally separated rats after additional chronic stress during adulthood. Maternal separation caused downregulation of neurotrophins in the ventral hippocampus, possibly as an effect of high corticosterone levels, but compensatory mechanisms against cell death may be involved as neurotrophin levels increased in the dorsal hippocampus. Decreased anti-oxidant potential of serum could have been an effect of downregulated neurotrophin levels. © 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society.