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Stress History and Pubertal Development Interact to Shape Hypothalamic-Pituitary-Adrenal Axis Plasticity

Laboratory of Neuroendocrinology, Rockefeller University (R.D.R., R.B., N.C., M.V., B.S.M.), New York, New York 10021; Department of Psychology, Arizona State University (R.B., C.D.C.), Tempe, Arizona 85287; and Department of Psychology, Columbia University (I.N.K.), New York, New York 10027

Address all correspondence and requests for reprints to: Dr. Russell D. Romeo, Laboratory of Neuroendocrinology, Rockefeller University, Box 165, New York, New York 10021. E-mail: romeor{at}rockefeller.edu.

Both the magnitude and the duration of the hormonal stress response change dramatically during neonatal development and aging as well as with prior experience with a stressor. However, surprisingly little is known with regard to how pubertal maturation and experience with stress interact to affect hypothalamic-pituitary-adrenal axis responsiveness. Because adolescence is a period of neurodevelopmental vulnerabilities and opportunities that may be especially sensitive to stress, it is imperative to more fully understand these interactions. Thus, we examined hormonal and neural responses in prepubertal (28 d of age) and adult (77 d of age) male rats after exposure to acute (30 min) or more chronic (30 min/d for 7 d) restraint stress. We report here that after acute stress, prepubertal males exhibited a significantly prolonged hormonal stress response (e.g. ACTH and total and free corticosterone) compared with adults. In contrast, after chronic stress, prepubertal males exhibited a higher response immediately after the stressor, but a faster return to baseline, compared with adults. Additionally, we demonstrate that this differential stress reactivity is associated with differential neuronal activation in the paraventricular nucleus of the hypothalamus, as measured by FOS immunohistochemistry. Using triple-label immunofluorescence histochemistry, we found that a larger proportion of CRH, but not arginine vasopressin, cells are activated in the arginine vasopressin in response to both acute and chronic stress in prepubertal animals compared with adults. These data indicate that experience-dependent plasticity of the hypothalamic-pituitary-adrenal neuroendocrine axis is significantly influenced by pubertal maturation.

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