The vasopressin V1b receptor modulates plasma corticosterone responses to dehydration-induced stress.

Vasopressin V1b receptor knockout (V1b⁻/⁻) mice were used to investigate a putative role for the V1b receptor (V1bR) in fluid regulation and in the hypothalamic-neurohypophysial system (HNS) and hypothalamic-pituitary-adrenal (HPA) axis responses to osmotic stress induced by water deprivation (WD). Male wild-type and V1b⁻/⁻ mice were housed in metabolic cages to allow determination of water intake and urine volume and osmolality. When provided with food and water ad lib., spontaneous urine volume and urine osmolality did not differ between genotypes. Similarly, WD for 24 h caused comparable decreases in urine volume and increases in urine osmolality irrespective of genotype. WD resulted in an increase in plasma corticosterone concentration in wild-type animals; however, this WD-induced increase in plasma corticosterone was significantly attenuated in V1b⁻/⁻ mice. Comparable increases in neuronal activation, indicated by increased c-fos mRNA expression, and in vasopressin mRNA expression occurred in both the supraoptic nucleus and paraventricular nucleus (PVN) of wild-type and V1b⁻/⁻ mice following WD; however, the WD-induced decrease in corticotrophin-releasing hormone mRNA expression seen in the PVN of wild-type mice was not observed in the PVN of V1b⁻/⁻ mice. These data suggest that, although the vasopressin V1bR is not required for normal HNS function, it is necessary for a full HPA-axis response to the osmotic stress of WD.