Heterogeneity of neuroendocrine stress responses in aging rat strains.

Hyperactivity of the hypothalamo-pituitary-adrenocortical (HPA) axis is linked with age-related decrements in cognition and neuronal survival. However, the nature and extent of age-related HPA axis deficits vary considerably across and indeed, within strains. The current study was designed to assess variance in HPA axis function using two rodent models commonly used in aging studies: Fischer 344 (F344) and F344/Brown-Norway F1 hybrid rats (F344/BN). We examined both basal and stress-induced ACTH and corticosterone (CORT) release in two stress contexts thought to differ in intensity: novel environment ('mild') and restraint ('intense'). Variability of the data was tested with a modification of the Brown-Forsythe test of homoscedasticity. The results indicated that F344 rats exhibit greater peak HPA responses. Furthermore, in most cases variability was increased in aged rats relative to young and middle-aged rats of the same strain, indicative of the emergence of individual differences in stress responsivity amongst older rats. The results suggest that these older rat strains may be useful models to further assess individual differences in neuroendocrine aging.

Stability of neuroendocrine and behavioral responsiveness in aging Fischer 344/Brown-Norway hybrid rats.

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.