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

Oxytocin is a classic reproductive neuropeptide in the female mammal, but i ts functions in the brain of the male have been less well studied. As stres s induces intracerebral oxytocin release independently of gender, we postul ated that central oxytocin may play a role in the control of stress respons es. In both male and virgin female rats, oxytocin receptor blockade in the brain by intracerebral infusion of a selective oxytocin antagonist (des Gly -NH2 d(CH2)(5) [Tyr(Me)(2), Thr(4)] OVT; 0.75 mu g/5 mu l increased the act ivity of the hypothalamo-pituitary-adrenal (HPA) axis as indicated by a sig nificantly enhanced basal and stress-induced (exposure to the elevated plus -maze, forced swimming) secretion of corticotropin (ACTH) and corticosteron e into blood. The anxiety-related behaviour on the plus-maze was not altere d by the antagonist in either males or females. Infusion of the oxytocin an tagonist into the hypothalamic paraventricular nucleus by reversed microdia lysis resulted in a significant increase in basal release of ACTH in both m ale and virgin female rats. These results demonstrate a novel, gender-indep endent physiological function of endogenous brain oxytocin in the regulatio n of neuroendocrine stress responses. Under basal conditions, the inhibitio n of the HPA axis occurs, at least in part, within the paraventricular nucl eus.