Alongside its classical physiological roles in maternal behaviour, oxytocin is now considered to be involved in the homeostatic control of food intake [1]. Its anorexigenic effects are thought to be evoked by peripheral satiety signals, including cholecystokinin and gastric distention [2]. Using c-Fos-like immunoreactivity and in vivo electrophysiology, we have developed a novel in vivo gut-brain signalling model to study the activity of oxytocin-releasing SON neurons in response to a palatable food delivered directly into the stomach. Adult male Sprague-Dawley rats were fasted overnight, anaesthetised (pentobarbital, 60mg/kg; ip), tracheotomised and the femoral vein cannulated (for anaesthesia maintenance (18.6mg/kg/hr) and blood sampling). A gavage tube was inserted orally into the stomach and 5ml of sweetened condensed milk (SCM) was infused (n=8). Blood was sampled and plasma collected before, during and after gavage. Precisely 1h after gavage, rats were perfused-fixed and the brains processed for c-Fos- and oxytocin-like immunoreactivity. Two control groups were subjected to a sham gavage (n=8) and gastric distention (inflated balloon attached to gavage tube; n=9). For in vivo electrophysiology, the ventral surface of the brain was exposed by transpharangeal surgery and a microelectrode inserted into the SON. Oxytocin cells were identified by their excitatory response to iv cholecystokinin (n=9). Extracellular recordings were made continuously during SCM gavage. After SCM gavage there was an increase in c-Fos expression in SON oxytocin neurons in comparison to sham gavage and gastric distention (p=0.04 and p=0.02 respectively, one-way ANOVA). There was no difference in c-Fos expression in SON oxytocin neurons between sham gavage and gastric distention (p=0.9, t-test). Identified oxytocin SON neurons showed a progressive increase in firing rate starting ~10 min after gavage onset (p<0.05, Kruskal-Wallis test (p=0.002)). Plasma osmolarity did not change before, during or after SCM gavage (p=0.12, two-way ANOVA). SCM gavage results in increased c-Fos-like immunoreactivity and a sustained increase in the firing rate of SON oxytocin neurons. This increase in SON neuron activity does not appear to be due to a change in osmolarity. Instead, SON oxytocin neurons may be regulated by satiety-related peripheral signals released in response to food in the stomach, providing further evidence for the role of oxytocin in the homeostatic control of food intake.