Corticotrophin-releasing factor receptor 2 mediates the enhanced activation of satiety-related responses through oxytocin neurons in the paraventricular nucleus of the hypothalamus after adrenalectomy

Adrenalectomy (ADX)-induced hypophagia is associated with increased activation of corticotrophin-releasing factor (CRF) and oxytocin (OT) neurons in the paraventricular nucleus of the hypothalamus (PVN) after refeeding. CRF2- and OT-receptor antagonists abolish the hypophagia and the augmented activation of the nucleus of the solitary tract neurons induced by feeding after ADX. In addition, OT-receptor antagonist reversed CRF-induced anorexia. We evaluated the effect of intracerebroventricular pretreatment with CRF2-receptor antagonist, antisauvagine-30 (AS30), on the activation of OT neurons of the PVN in response to refeeding of sham, adrenalectomized (ADX) and ADX rats replaced with corticosterone (ADX+B). In vehicle-pretreated animals, refeeding increased the number of Fos+OT double labeled neurons in the posterior parvocellular subdivision of the PVN (PaPo) of sham, ADX and ADX+B animals, with higher Fos expression and OT neuronal activation in the ADX group. AS30 reversed refeeding-induced increased activation of OT and non-OT neurons in the PaPo in the ADX group. In the medial parvocellular subdivision of the PVN (PaMP) of vehicle-pretreated animals, the number of Fos- and Fos+OT-immunoreactive neurons was increased after refeeding in ADX group. AS30 in the ADX group attenuated the enhanced Fos expression but not the number of Fos+OT double labeled neurons in the PaMP. In conclusion, CRF2-receptor antagonist reverses the increased activation of OT neurons in the PaPo induced by feeding in ADX animals, suggesting that OT neurons might be downstream mediators of CRF effects on satiety-related responses after ADX.