This study examined the behavioural and physiological effects of chronic mild stress on neonatally handled and non-handled rats. Neonatally handled and non-handled rats were exposed to chronic mild stress from weaning time to 6 months of age. They were behaviourally tested at 6 months of age, and sacrificed for analysis of nerve growth factor (NGF) in the hippocampus and hypothalamus. In contrast to the reported deleterious effect of acute strong stress, mild stress appeared to stimulate production of NGF in the hippocampus and improve spatial learning in both handled and nonhandled rats. Because neonatal handling produces neuroanatomical changes in the rat hippocampus and enhances cognitive function throughout the rats life span, these results implicate hippocampal NGF in the neuroprotective effects of handling.
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