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Stability of Neuroendocrine and Behavioral Responsiveness in Aging Fischer 344/Brown-Norway Hybrid Rats

Psychiatry Service (J.W.K.), Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio 45220; and Departments of Psychiatry (J.W.K., T.M.S., C.X., A.R.F., N.K.E., M.M.O., J.P.H.) and Surgery (C.X.), University of Cincinnati, Cincinnati, Ohio 45221

Address all correspondence and requests for reprints to: James P. Herman, Genomic Research Institute, 2170 East Galbraith Road, Building E, Room 216, Cincinnati, Ohio 45237. E-mail: hermanjs{at}ucmail.uc.edu.

Aging in rodents and primates is accompanied by changes in hypothalamic-pituitary-adrenal (HPA) activity. We examined behavioral and neuroendocrine responses in 3, 15-, and 30-month-old F344/Brown-Norway rats. Basal corticosterone and ACTH levels did not differ with age, although ACTH responses, but not corticosterone responses to restraint stress, were significantly lower in the 30-month-old group relative to 3- and 15-month-old rats. Induction of c-fos mRNA in the paraventricular nucleus from restraint was not affected by age. Furthermore, there was an enhanced sensitivity to dexamethasone suppression in aged animals as evidenced by lesser ACTH and corticosterone release after dexamethasone administration. Evaluation of emotional behaviors in the forced swim test revealed no differences between the age groups. With fear conditioning, aged rats had decreased freeze times relative to middle-aged or young rats. Regression analysis revealed no significant correlations between the behavioral and HPA axis data in any group. Overall, the data suggest that an apparent decrease in pituitary drive is compensated for at the level of the adrenal, resulting in stable patterns of glucocorticoid secretion. The lack of a correlation between HPA axis measures and emotional as well as fear conditioning-related behaviors indicates that corticosteroid dysfunction may not predict age-related behavioral deficits in this aging model.