Release of oxytocin within the supraoptic nucleus. Mechanisms, physiological significance and antisense targeting

In addition to its secretion from neurohypophysial terminals, oxytocin (OT) is released within the hypothalamic magnocellular nuclei--the supraoptic (SON) and paraventricular nuclei--in response to various stimuli as mainly shown by microdialysis studies. During parturition and suckling, OT is released within the SON in a positive feedback role to further amplify its own local and/or neurohypophysial release depending upon the reproductive conditions. Whereas, for instance, intra-SON OT is important for appropriate OT secretion and milk ejection during suckling, it seems to be involved in the timing of the parturition process without directly affecting OT secretion during birth. As a consequence of various morphological and physiological adaptations of the OT system during lactation, the release pattern of OT into blood and within the SON is altered in response to other stimuli, like swim stress and peripheral osmotic stimulation. In addition, in lactating, but not virgin female or male rats, unilateral stimulation of the SON results in the release of OT, but not vasopressin or various amino acids, within the contralateral SON, which implicates a functional role of intranuclear OT in the plastic coupling of the paired SON during lactation. To manipulate OT synthesis and release, antisense targeting was used. Novel, acute effects (within 5 hours) of an OT antisense oligodeoxynucleotide on suckling-related parameters and, specifically, on the electrophysiological excitability of OT neurons as well as their ability to express the Fos-protein after CCK-8 are described. Since the OT content in the hypothalamo-neurohypophysial system was still unaffected at this time, antisense oligonucleotides may induce feedforward alterations in neuronal responsiveness which precede or parallel effects on neuropeptide synthesis. Taken together, the functional significance of OT released within the brain and into blood during reproduction provides an example of how a neuropeptide might regulate complex physiological and behavioral performances in a synergistic manner.