Individual Differences in Stress Responsiveness of the Hypothalamic-Pituitary-Adrenal Axis and Its Vasopressinergic Regulation in Old Monkeys

Abstract

Stress adaptation is fundamental for health, and the hypothalamic-pituitary-adrenal axis (HPA) is one of its main mechanisms. Considerable data indicate that arginine vasopressin (AVP) related disturbances of stress adaptation can occur with aging. However, most studies of such kind have been performed on rodents, give contradictory results and fail to consider individual characteristics of the animals. The purpose of this study was to investigate individual HPA responsiveness to acute stress and its vasopressinergic regulation in old female rhesus monkeys that differ in their behavioral responses to stress. Animals with depression-like or anxiety-like behavior (DAB) responded with higher plasma levels of ACTH and AVP, lower levels of corticosteroids and higher cortisol/DHEAS molar ratios to restraint stress and to insulin-induced hypoglycemia compared with animals with healthy adaptive behavior. AVP and ACTH dynamics were closely correlated in most animals. AVP treatment produced differences in HPA responses similar to those produced by the stressors. The ACTH response to hypoglycemic stress in the DAB animal with highest HPA responsiveness was dramatically reduced by prior administration of a V1b receptor antagonist. These results suggest that the dysfunctions of HPA observed in old animals with DAB are caused by increased tone of the vasopressinergic system in regulation of HPA stress reactivity.

Glucocorticoid Negative Feedback in Regulation of the Hypothalamic-Pituitary-Adrenal Axis in Rhesus Monkeys With Various Types of Adaptive Behavior: Individual and Age-Related Differences

“…In addition, earlier we published data that the vast majority of adult and old female rhesus monkeys subjected to maternal deprivation in the early postnatal period show anxiety-like or depression-like behavior, as well as damage in the functioning of the HPA axis (73). Moreover, there is a definite correlation between our previously published studies (13, 14, 19) with the results of works (63, 74, 75), who demonstrated that women with a history of stress in the early period of life and without depression at the time of the survey demonstrate increased ACTH response to stress and CRH administration.…”

“…Hyperactivation of the HPA axis was detected in rodents with depression-like and anxiety-like behavior (8, 9), as well as in persons with depression (10, 16). Differences in the stress response of the HPA axis were observed in immature nonhuman primates with high and low trait anxiety (17) and in old female rhesus monkeys with depression-like and anxiety-like behavior, on the one hand, and usual standard behavior, on the other hand (13, 14). Thus, old animals with depression-like and anxiety-like behavior were most vulnerable to negative aspects of acute stress exposure and showed the greatest disturbances in the functioning of the HPA axis accompanied by an increase in the concentration of biomarkers of aging (13, 14).…”

“…Differences in the stress response of the HPA axis were observed in immature nonhuman primates with high and low trait anxiety (17) and in old female rhesus monkeys with depression-like and anxiety-like behavior, on the one hand, and usual standard behavior, on the other hand (13, 14). Thus, old animals with depression-like and anxiety-like behavior were most vulnerable to negative aspects of acute stress exposure and showed the greatest disturbances in the functioning of the HPA axis accompanied by an increase in the concentration of biomarkers of aging (13, 14). Significant differences in the functioning of the HPA axis were also demonstrated by young mature animals with depression-like and anxiety-like behavior (18–20).…”

“…Earlier, we obtained data to conclude that in old primates with depression-like and anxiety-like behavior the activity of specific vasopressin V1b receptors on corticotrophs of the anterior pituitary was increased. So, we supposed an increase in the activity of specific receptors to CRH (CRHRI) on corticotrophs of the pituitary gland (13, 18, 19, 21). In turn, an increase in the concentration of specific receptors on corticotrophs in individuals with depression-like and anxiety-like behavior could be a consequence of increased synthesis and secretion of CRH and AVP in the pituitary portal system.…”

“…Previously we proposed a natural animal model (female rhesus monkeys with standard, aggressive, depression-like, and anxiety-like behavior) to study individual differences in the functioning of HPA axis (12, 18). In addition, as mentioned above, we studied the intergroup and age-related features of HPA axis response to acute psycho emotional stress exposure in monkeys with standard, depression-like, and anxiety-like behavior (13, 14). These research revealed pronounced individual and age differences in the stress responsiveness of HPA axis.…”