Blunted HPA axis response in lactating, vasopressin-deficient Brattleboro rats.

Adaptation to stress is a basic phenomenon in mammalian life that is mandatorily associated with the activity of the hypothalamic-pituitary-adrenal (HPA) axis. An increased resting activity of the HPA axis can be measured during pregnancy and lactation, suggesting that these reproductive states lead to chronic load in females. In this study, we examined the consequences of the congenital lack of vasopressin on the activity of the HPA axis during lactation using vasopressin-deficient Brattleboro rats. Virgin and lactating, homozygous vasopressin-deficient rats were compared with control, heterozygous rats. In control dams compared with virgins, physiological changes similar to those observed in a chronic stress state (thymus involution, adrenal gland hyperplasia, elevation of proopiomelanocortin mRNA levels in the adenohypophysis, and resting plasma corticosterone levels) were observed. In vasopressin-deficient dams, adrenal gland hyperplasia and resting corticosterone level elevations were not observed. Corticotropin-releasing hormone (Crh) mRNA levels in the hypothalamic paraventricular nucleus were elevated in only the control dams, while oxytocin (OT) mRNA levels were higher in vasopressin-deficient virgins and lactation induced a further increase in both the genotypes. Suckling-induced ACTH and corticosterone level elevations were blunted in vasopressin-deficient dams. Anaphylactoid reaction (i.v. egg white) and insulin-induced hypoglycemia stimulated the HPA axis, which were blunted in lactating rats compared with the virgins and in vasopressin-deficient rats compared with the controls without interaction of the two factors. Vasopressin seems to contribute to the physiological changes observed during lactation mimicking a chronic stress state, but its role in acute HPA axis regulation during lactation seems to be similar to that observed in virgins. If vasopressin is congenitally absent, OT, but not the CRH, compensates for the missing vasopressin; however, the functional restitution remains incomplete.

The role of vasopressin in chronic stress studied in a chronic mild stress model of depression.

BACKGROUND AND PURPOSE: Vasopressin plays an important role in the hypothalamo-pituitary-adrenal axis regulation as well as in stress-related disorders. A common view suggested that the role of vasopressin is especially important during chronic stresses. Here we tested the hypothesis that vasopressin-deficient rats may be more resistant to the development of chronic hypothalamo-pituitary-adrenal axis hyperactivity after chronic mild stress. METHODS: Male vasopressin deficient Brattleboro rats were compared to their heterozygous litter mates. Chronic mild stress consisted of different mild stimuli (e.g. wet cages, restraint) for 6 week. The corticosterone changes were followed by repeated tail cutting and organs and blood were collected from decapitated rats. RESULTS: In controls, chronic mild stress resulted in symptoms of chronic stress state characterized by typical somatic (body weight reduction, thymus involution) and endocrine changes (resting plasma ACTH and corticosterone elevation and POMC mRNA elevation in anterior lobe of the pituitary). Unexpectedly, the lack of vasopressin could not influence any chronic mild stress-induced changes. CONCLUSION: Somatic changes and endocrine effects of chronic mild stress are similar in control and vasopressin deficient animals. This suggests that either vasopressin is not indispensable for activating the hypothalamo-pituitary-adrenal axis by chronic stress or the absence of vasopressin is compensated by other mediators (e.g. CRH) in Brattleboro rats.