Oxytocin projections to the nucleus of the solitary tract contribute to the increased meal-related satiety responses in primary adrenal insufficiency.

Anorexia is a common clinical manifestation of primary adrenal gland failure. Adrenalectomy (ADX)-induced hypophagia is reversed by oxytocin (OT) receptor antagonist and is associated with increased activation of satiety-related responses in the nucleus of the solitary tract (NTS). This study evaluated OT projections from the paraventricular nucleus of the hypothalamus (PVN) to the NTS after ADX and the effect of pretreatment with intracerebroventricular injection of an OT receptor antagonist ([d(CH2)5,Tyr(Me)(2),Orn(8)]-vasotocin; OVT) on the activation of NTS neurons induced by feeding in adrenalectomized rats. Adrenalectomized animals showed higher OT labelling in the NTS than the sham and the ADX with corticosterone replacement (ADX + B) groups. Adrenalectomized animals exhibited co-localization of the anterograde tracer Phaseolus vulgaris leucoagglutinin and OT in axons in the NTS as well as OT fibres apposing NTS neurons activated by refeeding. After vehicle pretreatment, compared with fasting, refeeding increased the numbers of Fos- and Fos + TH-immunoreactive neurons in the NTS in sham, ADX and ADX + B groups, with a higher number of these immunolabelled neurons in adrenalectomized animals. Compared with fasting conditions, refeeding also increased the activation of NTS neurons in OVT-pretreated sham, ADX and ADX + B groups, but there was no difference among the three experimental groups. These data demonstrate that OT is upregulated in projections to the NTS following ADX and that OT receptor antagonist reverses the greater activation of NTS neurons induced by feeding after ADX. The data indicate that OT pathways to the NTS contribute to higher satiety-related responses and, thus, to reduce meal size in primary adrenal insufficiency.