BACKGROUND: Adrenalectomy does impair the expression of hypothalamic NPY gene in the rat and replacement of glucocorticoid by intracerebroventricular(ICV) route resulted in a normalization of refeeding hyperphagia and weight gain in adrenalectomized(ADX), food-deprived rats. The purpose of this study was to assess the direct effect of CNS glucocorticoid on hypothalamic NPY gene expression which occurs following food deprivation in ADX rats. METHODS: Adult male Wistar rats were fitted with ICV cannulae and restricted the food intake for 14 days. Adrenalectomy and sham operation were done on the 10th day and single ICV corticosterone acetate(100ug/2uL) was given in one ADX group(ADX+CORT, n=9) and vehicle (2uL) was given in another ADX group(ADX+VEH, n=9) and sham rats(SHAM+VEH, n=7). After experiment, we measured NPY mRNA on arcuate nucleus by in situ hybridization. RESULTS: The rate of weight loss of ADX rats closely parallded that of sham-operated rats. Plasma glucose and insulin levels were not significantly different in three groups. Hybridization density on the ARC in ADX+VEH rats(0.42+/-0.02uCi/g: p<0.05) was significantly reduced compared to that in sham controls(0.68+/-0. 11uCi/g). ICV corticosterone injection increased the hybridization density in ADX+CORT rats(0.53+/-0.04uCi/g) compared to vehicle alone, although this did not reach that of controls. NPY gene expression was 40% in ADX+VEH rats and 62% in ADX+CORT rats compared to control rats. CONCLUSIONS: These results are consistent with the hypothesis that CNS glucocorticoid deficiency appears to be responsible for the impairment of refeeding hyperphagia in ADX rats and the effect of CNS glucocorticoid deficiency is a manifestation of impaired activation of hypothalamic NPY gene expression in the ARC.