Effect of vasopressin 1b receptor blockade on the hypothalamic–pituitary–adrenal response of chronically stressed rats to a heterotypic stressor

Abstract

Exposure to chronic restraint (CR) modifies the hypothalamicpituitary-adrenal (HPA) axis response to subsequent acute stressors with adaptation of the response to a homotypic and sensitization of the response to a heterotypic stressor. Since vasopressin (AVP) activity has been reported to change during chronic stress, we investigated whether this was an important factor in HPA facilitation. We therefore tested whether vasopressin 1b receptor (AVPR1B) blockade altered the ACTH and corticosterone response to heterotypic stressors following CR stress. Adult male rats were exposed to CR, single restraint, or were left undisturbed in the home cage. Twentyfour hours after the last restraint, rats were injected with either a AVPR1B antagonist (Org, 30 mg/kg, s.c.) or vehicle (5% mulgofen in saline, 0 . 2/kg, s.c.) and then exposed to either restraint, lipopolysaccharide (LPS) or white noise. CR resulted in the adaptation of the ACTH and corticosterone response to restraint and this effect was not prevented by pretreatment with Org. Although we found no effect of CR on LPS-induced ACTH and corticosterone secretion, both repeated and single episodes of restraint induced the sensitization of the ACTH, but not corticosterone response to acute noise. Pretreatment with Org reduced the exaggerated ACTH response to noise after both single and repeated exposure to restraint.

Acute stress‐induced sensitization of the pituitary–adrenal response to heterotypic stressors: Independence of glucocorticoid release and activation of CRH1 receptors

“…Long-lasting HPA sensitization after acute exposure appears to be a characteristic of severe stressors. For instance, restraint, which is clearly less severe than IMO (Campmany et al, 1996;Martí et al, 2001;Rabasa et al, 2011), did not cause sensitization of the HPA response to an additional stressor on the day after in non-treated rats (Wong et al, 2000) or the effects are small (Spiga et al, 2009). However, Wong et al (2000) demonstrated that blockade of restraint-induced corticosterone release with aminoglutethimide, an inhibitor of glucocorticoid synthesis, did result in sensitization of the HPA response to a further stressor.…”

“…However, the factors involved in the induction of long-lasting stress-induced HPA sensitization are not known. Vasopressin (AVP) may be involved in the expression of acute stress-induced sensitization as blockade of AVP type 1b receptors blunted the slight sensitization of the ACTH response to noise observed on the day after a single exposure to restraint (Spiga et al, 2009).…”

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…In another forced swimming test, plasma levels of corticosterone, but not ACTH, were elevated 105 min after the onset of stress only in Brattleboro rats (551). Other types of acute stress have also been examined (313,314,424,430,462,468,469,554). In insulin-induced hypoglycemia stress, but not acute restraint stress, an increase in plasma ACTH and corticosterone levels was attenuated in V1bR-KO mice (313).…”

“…The V1b receptor antagonist Org suppressed increases of ACTH secretion evoked by acute restraint, lipopolysaccharide (LPS) administration, and acute noise stress (103,462). Water deprivation for 24 h also increased the plasma corticosterone level, and this increase was significantly attenuated in V1bR-KO mice (424).…”

“…Other studies suggest potential applications of V1b antagonists for treating ACTH-secreting tumors, Cushing's syndrome, and gastrointestinal diseases (30,109,152,283). ORG52186 has recently been reported to be a selective V1b receptor antagonist (103,296), and it has been found to be effective in animal models for suppressing stress responses mediated by the pituitary V1b receptor (430,462,463).…”