Refeeding-induced expression of neuronal nitric oxide synthase in the rat paraventricular nucleus

We have previously reported that food deprivation decreases the expression of neuronal nitric oxide synthase (nNOS) in the hypothalamic paraventricular nucleus (PVN) of rats, and this reduction is inhibited by blockade of glucocorticoid receptors. In this study, we examined whether the fasting-induced decrease in nNOS gene expression in the PVN is restored by refeeding. The number of nNOS immunopositive cells in the PVN, which was markedly decreased by 48 h of food deprivation, increased significantly after 6 h of refeeding and was fully restored by 24 h after refeeding. The plasma corticosterone level, which was markedly increased by food deprivation, decreased significantly within 30 min after refeeding and returned to the free fed control level by 6 h. Synthetic glucocorticoid dexamethasone blocked the refeeding-induced nNOS expression in the PVN without suppressing food intake. Refeeding with a non-caloric food mash for 5 h failed to restore the fasting-induced decrease in the PVN-nNOS but did, however, successfully restore the plasma corticosterone level. These results suggest that the refeeding-induced nNOS expression in the PVN is a nutrient-directed event and that plasma glucocorticoids may play an inhibitory role in the regulatory pathway. Additionally, glucocorticoid disinhibition alone does not appear to be sufficient to induce nNOS expression in the PVN; nNOS expression in the PVN upon refeeding may require both nutrient supplementation and glucocorticoid disinhibition.