Brain Oxytocin Inhibits Basal and Stress‐Induced Activity of the Hypothalamo‐Pituitary‐Adrenal Axis in Male and Female Rats: Partial Action Within the Paraventricular Nucleus

TLDR

Oxytocin, a reproductive neuropeptide well studied in females, has poorly understood central roles in males, and basal inhibition of the HPA axis partly occurs in the paraventricular nucleus. The study aimed to test whether central oxytocin modulates stress‑induced HPA activity. The authors infused a selective oxytocin antagonist intracerebrally, including into the paraventricular nucleus, to block oxytocin receptors and assess resulting changes in basal and stress‑induced HPA activity. Blocking central oxytocin receptors elevated basal and stress‑induced ACTH and corticosterone secretion without affecting anxiety behavior, revealing a gender‑independent role for endogenous oxytocin in dampening HPA axis activity.

Abstract

Oxytocin is a classic reproductive neuropeptide in the female mammal, but its functions in the brain of the male have been less well studied. As stress induces intracerebral oxytocin release independently of gender, we postulated that central oxytocin may play a role in the control of stress responses. In both male and virgin female rats, oxytocin receptor blockade in the brain by intracerebral infusion of a selective oxytocin antagonist (des Gly‐NH 2 d(CH 2 ) 5 [Tyr(Me) 2 , Thr 4 ] OVT; 0.75 μg/5 μl increased the activity of the hypothalamo‐pituitary‐adrenal (HPA) axis as indicated by a significantly enhanced basal and stress‐induced (exposure to the elevated plus‐maze, forced swimming) secretion of corticotropin (ACTH) and corticosterone into blood. The anxiety‐related behaviour on the plus‐maze was not altered by the antagonist in either males or females. Infusion of the oxytocin antagonist into the hypothalamic paraventricular nucleus by reversed microdialysis resulted in a significant increase in basal release of ACTH in both male and virgin female rats. These results demonstrate a novel, gender‐independent physiological function of endogenous brain oxytocin in the regulation of neuroendocrine stress responses. Under basal conditions, the inhibition of the HPA axis occurs, at least in part, within the paraventricular nucleus.