Effects of repeated restraint stress on hypothalamo-pituitary-adrenocortical function in vasopressin deficient Brattleboro rats.

Arginine-vasopressin (AVP) has been proposed to be an important mediator during chronic stress in the regulation of the hypothalamo-pituitary-adrenal axis. In the present study we addressed the role of AVP in maintaining adrenocortical responsiveness during chronic stress using the AVP deficient mutant Brattleboro rat. Heterozygous Brattleboro rats (di/+) served as controls and were compared to homozygous rats (di/di) with diabetes insipidus. Sixty minutes daily restraint was repeated for 5, 8, 11 or 15 days and organ weights, plasma adrenocorticotropin (ACTH) and corticosterone levels and anterior pituitary proopiomelanocortin (POMC) mRNA and ACTH content were measured. The body, adrenal and thymus weight changes induced by chronic stress became significant between 5 and 8 repetition and AVP deficiency had no effect on these parameters. The first indication that AVP has a role to play appears after 11 repetitions. In the di/di group at the end of 11th restraint, the plasma ACTH was decreased when compared to the di/+ rats. In animals with indwelling cannulas some adaptation could be seen in ACTH response without any difference between di/+ and di/di rats after 15 restraints. The corticosterone- and prolactin-elevations induced by restraint did not habituate in the di/+ and the di/di rats. Chronic stress increased POMC mRNA in the anterior pituitary similarly in di/+ and di/di rats. Although AVP seems to be necessary for a full ACTH response, most of the other signs of chronic stress after repeated restraint occur unchanged in the absence of AVP in both genders. This suggests that either AVP is not indispensable for activating the hypothalamo-pituitary-adrenocortical system by chronic stress or the absence of AVP is compensated by other mediators in Brattleboro rats.