Vasopressin Administration into the Paraventricular Nucleus Normalizes Plasma Oxytocin and Corticosterone Levels in Brattleboro Rats

Abstract

Adult male rats of the Brattleboro strain were used to investigate the impact of the congenital absence of vasopressin on plasma adrenocorticotropin, corticosterone, and oxytocin concentrations as well as the release pattern of oxytocin within the hypothalamic paraventricular nucleus (PVN), in response to a 10-min forced swimming session. Measurement of adrenocorticotropin in plasma samples collected via chronically implanted jugular venous catheters revealed virtually identical stress responses for vasopressin-lacking Brattleboro (KO) and intact control animals. In contrast, plasma corticosterone and oxytocin levels were found to be significantly elevated 105 min after onset of the stressor in KO animals only. Microdialysis samples collected from the extracellular fluid of the PVN showed significantly higher levels of oxytocin both under basal conditions and in response to stressor exposure in KO vs. intact control animals accompanied by elevated oxytocin mRNA levels in the PVN of KO rats. These findings suggest that the increased oxytocin levels in the PVN caused by the congenital absence of vasopressin may contribute to normal adrenocorticotropin stress responses in KO animals. However, whereas the stressor-induced elevation of plasma oxytocin in KO rats may be responsible for their maintained corticosterone levels, oxytocin seems unable to fully compensate for the lack of vasopressin. This hypothesis was tested by retrodialyzing synthetic vasopressin into the PVN area concomitantly with blood sampling in KO animals. Indeed, this treatment normalized plasma oxytocin and corticosterone levels 105 min after forced swimming. Thus, endogenous vasopressin released within the PVN is likely to act as a paracrine signal to facilitate the return of plasma oxytocin and corticosterone to basal levels after acute stressor exposure.

The stimuli-specific role of vasopressin in the hypothalamus–pituitary–adrenal axis response to stress

“…The structurally related other nonapeptide oxytocin, is another possible candidate which can act also on V1b receptors (Schlosser et al 1994). In our recent study, we have established that although oxytocin mRNA level is elevated in the PVN, the functional replacement remained incomplete (Zelena et al 2009). The adjacent stress regulatory system, the sympatho-adrenomedullary axis is also functioning at an elevated level in homozygote Brattleboro rats (Kvetnansky et al 1990).…”

Increase in Alzheimer's related markers preceeds memory disturbances: Studies in vasopressin-deficient Brattleboro rat

“…We compared the AVP deficient homozygous recessive (di/di) rats with diabetes insipidus to normal homozygous dominant (+/+) control rats [68]. As Brattleboro rats originated from Long Evans strain approx.…”

“…50 years ago, it is not a proper control for AVP-deficiency. Our control, +/+ rats were bread out locally [68]. They are in close relationship with the AVP-deficient ones (heterozygous mothers are the daughters of +/+ mothers).…”

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

“…The concentrations of ACTH and corticosterone were measured using RIA, as described previously (Zelena et al 2009b). The intra-assay coefficients of variation for ACTH and corticosterone were 4.7 and 12.3% respectively.…”