Age-Specific and Individual Features of Vasopressinergic Regulation of the Hypothalamic–Pituitary–Adrenal System in Primates

Abstract

Experimental study was carried out on young mature (6-8 years) and old (21-27 years) rhesus macaques with anxious and depression-like behavior and with standard (control) adaptive behavior. The responce of the adenohypophysis to arginine vasopressin depended on age and the type of adaptive behavior. Young animals with standard behavior demonstrated much higher concentrations of ACTH in the peripheral plasma in response to arginine vasopressin than old animals. The secretion of ACTH was higher in young and old animals with anxious and depressive-like adaptive behavior and they exhibited no age-specific differences in reaction to arginine vasopressin, which were observed in control animals. Preinjection of vasopressin V1b receptor antagonist to a female with high anxiety sharply reduced ACTH secretion in response to insulin-induced hypoglycemia in comparison with ACTH secretion under the same conditions without antagonist injection. These results suggested that the vasopressinergic system of animals with anxious and depressive behavior plays an important role in the regulation of ACTH secretion and in activity of the hypothalamic-pituitary-adrenal system in general.

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

“…Several studies have shown that age-related dysfunctions of the HPA axis of nonhuman primates are related to the adaptive behavior patterns of the animals [3] [4] [12] [13]. The most pronounced age-related dysfunctions observed in female rhesus monkeys with depression-like and anxiety-like behavior as compared with monkeys with standard adaptive behavior [3] [4] [12] [13] [22]. Pronounced disturbances of the HPA axis similar to those identified in nonhuman primates were found in elderly male patients with depression [23].…”

“…Experimental data suggest an important role of AVP in the regulation of HPA axis stress reactivity and depression-like and anxiety-like behavior [22] [28]. For example, recent experiments on female rhesus monkeys demonstrated different age-related changes in reaction of the adenohypophysis to AVP administration in female rhesus monkeys with various types of behavior [22].…”

“…Experimental data suggest an important role of AVP in the regulation of HPA axis stress reactivity and depression-like and anxiety-like behavior [22] [28]. For example, recent experiments on female rhesus monkeys demonstrated different age-related changes in reaction of the adenohypophysis to AVP administration in female rhesus monkeys with various types of behavior [22]. While ACTH secretion did not change in response to AVP injection in old monkeys with depression-like and anxiety-like behavior as compared with young monkeys with the same behavior, it decreased in old monkeys with standard adaptive behavior compared with young ones of the same behavior [22].…”

“…For example, recent experiments on female rhesus monkeys demonstrated different age-related changes in reaction of the adenohypophysis to AVP administration in female rhesus monkeys with various types of behavior [22]. While ACTH secretion did not change in response to AVP injection in old monkeys with depression-like and anxiety-like behavior as compared with young monkeys with the same behavior, it decreased in old monkeys with standard adaptive behavior compared with young ones of the same behavior [22]. These data suggest that age-related changes in the tone of the vasopressinergic system in the regulation of HPA axis stress reactivity in animals with various types of behavior are different and, perhaps, underlie individual differences in vulnerability of the HPA axis to stress and aging.…”

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

“…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). In these animals, an increased ACTH response to repeated stress exposure and also to functional tests with arginine vasopressin (AVP) and corticotrophin releasing hormone (CRH) was revealed compared to young females with standard behavior (18–20).…”