(FS), AVP is released somato-dendritically within the supraoptic nucleus (SON) and paraventricular nucleus (PVN), but not from neurohypophyseal terminals into blood. Together with AVP, oxytocin (OXT) is released within the SON and PVN. Here, we studied the role of intra-SON and intra-PVN OXT in the regulation of local AVP release and into the blood in male rats. Within the SON, bilateral retrodialysis of an OXT receptor antagonist (OXT-A) increased local AVP release in response to FS [60 s, 21°C, vehicle twofold, not significant (ns); OXT-A: 15-fold increase, P Ͻ 0.05] without significantly affecting basal AVP release. In addition, local OXT-A elevated plasma AVP secretion under basal conditions (twofold increase, P Ͻ 0.05) without further elevation after FS. Within the PVN, exposure to FS elevated local AVP release, reaching significance only in the OXT-A group (vehicle: 1.4-fold, ns; OXT-A: 1.6-fold increase, P ϭ 0.050). Bilateral OXT-A into the PVN did not affect peripheral AVP secretion either under basal or stress conditions. Basal ACTH concentrations tended to be elevated by local OXT-A within the PVN (1.7-fold increase, P ϭ 0.076). In contrast, the swim-induced ACTH secretion was attenuated after retrodialysis of OXT-A within both the SON (at 5 min) and PVN (at 15 min) (P Ͻ 0.05 both) compared with vehicle. The results demonstrate a receptormediated effect of OXT within the SON and PVN on local and neurohypophyseal AVP release, which depends upon the activity conditions. Further, while exerting an inhibitory effect on hypothalamo-pituitary-adrenal axis activity under basal conditions, hypothalamic OXT is essential for an adequate acute ACTH response.plasma; hypothalamo-pituitary-adrenal axis; dendritic release; microdialysis; swim stress THE NEUROPEPTIDES OXYTOCIN (OXT) and AVP are mainly synthesized in magnocellular neurons of the hypothalamic supraoptic nucleus (SON) and the paraventricular nucleus (PVN). They are released from neurohypophyseal axon terminals directly into the systemic circulation, but also in a somatodendritic fashion within the hypothalamus in response to relevant physiological stimuli, including parturition, suckling, osmotic challenge, and hemorrhage (for a review, see Ref. 33).Similarly, such local release within the SON and PVN has been described for both peptides, for instance, in response to various psychological stressors, such as forced swimming in male and female rats (for a review, see Ref. 16). However, upon stressor exposure, only OXT is simultaneously released from the dendrites within the hypothalamic nuclei and from neurohypophyseal terminals into blood, as revealed by intracerebral microdialysis in conjunction with blood sampling in conscious rats. In contrast, AVP secretion into blood remains unchanged despite its release within the PVN, SON, and/or septum, for example, during forced swimming or exposure to social defeat (13,14,44,60,61).The phenomenon of independent release patterns of AVP from dendrites within the SON/PVN and from neurohypophyseal terminals, in par...