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Vasopressin and oxytocin are released into the extracellular space of the supraoptic (SON) and paraventricular nuclei (PVN). The dendrites of these neurones contain a high density of neurosecretory granules, and exocytotic profiles have been visualised by electron microscopy. Release within the SON has been measured using microperfusion techniques; release is tetrodotoxin-independent, calcium-dependent, and is activated by a range of physiological stimuli, including suckling, dehydration, haemorrhage and stress. Release of vasopressin into the SON is regulated by a number of forebrain and brainstem areas. Dendritic release does not necessarily parallel neurohypophyseal release, and may occur semi-independently of spike activity in the soma and axons. The physiological consequences of dendritic vasopressin release are not clear, vasopressin and oxytocin appear to induce further vasopressin and oxytocin release from the dendrites. In contrast, by combining retrodialysis and electrophysiology we have shown that, unlike oxytocin which excites oxytocin neurones, vasopressin inhibits the electrical activity of vasopressin neurones, and hence suppresses vasopressin release from the pituitary. Thus, vasopressin released from dendrites may act on vasopressin neurones to regulate their phasic activity by an auto-inhibitory action within the SON. Since dendritic vasopressin release is increased and prolonged after various stimuli, this mechanism may act to restrain excitation of vasopressin neurones (and hence vasopressin secretion from the neurohypophysis) during continuing stimulation.

The nucleus tractus solitarii (NTS) projects directly to the oxytocin neurones of the supraoptic nucleus (SON), and relays afferent stimuli arising from the birth canal during parturition. About 80% of these projecting neurones are noradrenergic, and these same neurones are activated following systemic administration of cholecystokinin (CCK), which also results in an increased electrical and secretory activity in oxytocin neurones. Oxytocin release in response to CCK is abolished following selective neurotoxic destruction of these noradrenergic neurones. Oxytocin release following CCK (and that during parturition) is potently inhibited by morphine, which blocks the local noradrenaline release in the supraoptic nucleus. This acute opiate action involves presynaptic inhibition of the noradrenergic terminals, and occurs without marked suppression of the activity of noradrenergic cells in the NTS. During chronic exposure to morphine the oxytocin system becomes tolerant to, and dependent upon morphine. In the course of tolerance, oxytocin cell activation in response to CCK recovers from initial inhibition. However, the pathway that mediates this response does not appear to become dependent: the oxytocin cell response to CCK is unchanged by opiate withdrawal induced by naloxone, despite a large increase in the background electrical activity of oxytocin cells provoked by withdrawal. Nevertheless, expression of withdrawal excitation by oxytocin neurones is curiously contingent upon the activity of the noradrenergic input in that prior lesioning of this input has no effect upon the subsequent withdrawal excitation of oxytocin cells. Yet under urethane anaesthesia, acute pharmacological blockade of the noradrenergic input suppresses withdrawal. We discuss how these paradoxical observations might be reconciled, and note that the difference may be related to differing levels of tonic activity in the noradrenergic input. It is possible that dependence relies upon the input when it is there, but not when it is not.