Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats.

Animal studies on the effects of chronic variable stress during the peripubertal-juvenile period on hippocampal structure and function are lacking. Twenty-eight-day-old Sprague-Dawley rats were subjected to random, variable physical or social stress regimens for 4 weeks. Hippocampal volume was found to continue to grow in all lamina examined during the transition into young adulthood. Our variable physical stress paradigm led to inhibition of this growth in the CA1 pyramidal cell layer (PCL) and in the dentate gyrus-granular cell layer (DG-GCL), which reached full arrest in the CA3-PCL. Volume deficits were first observed after chronic stress exposure when 3 weeks, but not 24 h, of recovery had elapsed. Moreover, these volume deficits were associated with impairments in the Morris water-maze navigation, sustained down-regulation in the basal hippocampal glucocorticoid receptor gene expression, and deficits in the shutdown of acute stress-induced corticosterone secretion. Volume changes both due to normal maturation and after chronic stress exposure were independent of neuron number. Thus, a peripubertal-juvenile chronic stress paradigm that leads to significant alterations in the limbic-hypothalamic-pituitary-adrenal axis can produce robust effects in hippocampal structure and cognitive ability, lasting into adulthood.