Attenuated stress response to acute lipopolysaccharide challenge and ethanol administration in vasopressin V1b receptor knockout mice.

The arginine vasopressin (Avp) 1b receptor (Avpr1b) present on anterior pituitary corticotrophs is involved in the stimulation of adrenocorticotrophic hormone (ACTH) secretion, especially during times of stress. Corticotrophin-releasing hormone (CRH) is considered the major ACTH secretagogue during acute stress whereas Avp appears to be the more dominant mediator of the hypothalamic-pituitary-adrenal (HPA) axis response during chronic stress situations. To investigate the role of the Avpr1b in the HPA axis response to acute stress, we measured ACTH and corticosterone (CORT) plasma levels in Avpr1b knockout (KO) mice and wild-type controls in response to bacterial lipopolysaccharide (LPS) challenge and ethanol (EtOH) administration. Mice deficient in Avpr1b had markedly compromised plasma ACTH and CORT responses to acute (30 min) LPS, but normal ACTH and CORT response to more extended exposure (4 h) to the immune system activator. The plasma ACTH and CORT levels stimulated by intoxicating, sedative doses of EtOH (3.2 and 4 g/kg) were significantly decreased in the Avpr1b KO mice compared to wild-type littermates. Significantly higher EtOH-induced plasma ACTH and CORT secretion was measured in female than in male Avpr1b wild-type mice. There were no differences in the blood alcohol levels following acute EtOH administration in Avpr1b KO or wild-type mice of either gender. Our results clearly suggest that Avpr1b plays a significant role in the HPA axis response to acute immune stress and EtOH intoxication.

Pituitary-adrenal response to acute and repeated mild restraint, forced swim and change in environment stress in arginine vasopressin receptor 1b knockout mice.

Arginine vasopressin and corticotrophin-releasing hormone synthesised and released from the hypothalamic paraventricular nucleus are the prime mediators of the hypothalamic-pituitary-adrenal (HPA) axis response to stress. These neurohormones act synergistically to stimulate adrenocorticotophin (ACTH) secretion from the anterior pituitary, culminating in an increase in circulating glucocorticoids. Arginine vasopressin mediates this action at the arginine vasopressin 1b receptor (Avpr1b) located on pituitary corticotrophs. Arginine vasopressin is regarded as a minor ACTH secretagogue in rodents but evidence suggests that it has a role in mediating the neuroendocrine response to some acute and chronic stressors. To investigate the role of the Avpr1b in the HPA axis response to an acute and chronic (repeated) stress, we measured the plasma ACTH and corticosterone concentrations in three stress paradigms in both Avpr1b knockout and wild-type mice. Single acute exposure to restraint, forced swim and change in environment stressors elevated both plasma ACTH and corticosterone concentrations in wild-type animals. Conversely, the ACTH response to the acute stressors was significantly attenuated in Avpr1b knockout mice compared to their wild-type counterparts. Plasma corticosterone concentrations were reduced in Avpr1b knockout mice in response to change in environment but not to mild restraint or forced swim stress. Irrespective of genotype, there was no difference in the plasma ACTH or corticosterone concentrations in response to acute and repeated stressors. The data show that a functional Avpr1b is required for an intact pituitary ACTH response to the acute and chronic stressors used in this study. Furthermore, the normal corticosterone response to repeated exposure to change in environment stress also requires the Avpr1b to drive HPA axis responsiveness.