Microdialysis sampling was used to measure noradrenaline, dopamine and serotonin release in the supraoptic and paraventricular nuclei of urethane-anaesthetized rats following intravenous injection of 20 pglkg cholecystokinin. This dose of cholecystokinin stimulates oxytocin release from the posterior pituitary, while slightly inhibiting vasopressin release. Dialysis probes were placed in the paraventricular nucleus, and into dorsal or ventral regions of the supraoptic nucleus. Samples were collected at 10-min intervals in each animal before, during and after two injections of cholecystokinin, and following a control injection of 0.9% NaCI.The injections of cholecystokinin stimulated significant increases in the concentrations of noradrenaline, dopamine and serotonin in the paraventricular nucleus and of noradrenaline and serotonin in the dorsal supraoptic nucleus region. Conversely, in the ventral supraoptic nucleus region a significant reduction in noradrenaline release was observed, but dopamine and serotonin concentrations were not significantly affected. The control injections did not alter noradrenaline, dopamine or serotonin release.In the rat, peripheral injections of cholecystokinin octapeptide (CCK) result in a transient increase in the plasma concentration of oxytocin and a small reduction in plasma vasopressin concentration (1-3). Systemic injections of CCK increase the electrical activity of magnocellular oxytocin cells in the hypothalamus (4), and this action of CCK is apparently mediated via activation of the gastric vagus (2). Although the supraoptic nucleus (SON) contains a high density of specific binding sites for CCK (5), and SON neurons in vitro are excited by bath application of CCK (6), the SON and the paraventricular nucleus (PVN) are within the blood-brain barrier, which in general excludes blood-borne peptides. Direct application of CCK can induce the release of both vasopressin and oxytocin from the isolated neural lobe in vitro (7), but since gastric vagotomy abolishes the oxytocin response to systemic CCK (2)-and lesions in the vicinity of the area postrema attenuate the response (8), it is likely that the principal action of systemically-administered CCK is mediated via the nucleus tractus solitarius, which is adjacent to the area postrema, receives an extensive input from the dorsal motor nucleus of the vagus, and projects both directly, and indirectly via the ventrolateral medulla, to the SON and PVN (9). In particular, there are strong noradrenergic projections from the AI cell group in the ventrolateral medulla, and from the A2 cell group in the nucleus tractus solitarius to the vicinity of the SON and PVN (9-1 5). Noradrenaline is predominantly excitatory to both oxytocin and vasopressin magnocellular neurons (13-16). We have previously shown, using microdialysis sampling, that noradrenaline and serotonin concentrations are increased in the area of the SON following haemorrhage (17). In the present study we used microdialysis sampling followed by HPLC with electrochemica...