It is well established that histaminergic neurons densely innervate the anterior hypothalamus and regulate several functions through histamine H(1) receptor (H1R). However, functional innervations of histaminergic neurons in the caudal hypothalamus have been poorly investigated. Recently, we have demonstrated that c-Fos, a marker of neuronal activation, was significantly induced by food deprivation under scheduled feeding in H1R-expressing cells in the caudal part of the arcuate nucleus of hypothalamus (cARC) of rats and histaminergic neurons innervating this area. In this study, we have examined the functional involvement of histaminergic neurons in the food deprivation-induced c-Fos expression in the cARC under scheduled feeding. The c-Fos expression in the cARC by food deprivation was significantly suppressed by pretreatment with antihistamines. After food deprivation, the number of c-Fos-histidine decarboxylase (HDC) double-positive neurons was mostly increased in the E3 subdivision of the tuberomammillary nucleus (TM). Under the restricted feeding schedule, significant expressions of c-Fos were detected in the TM and cARC only when rats strongly anticipated feeding, compared with a slight c-Fos induction in both nuclei when they were satiated. These findings suggest that the histaminergic neurons in the E3 subdivision of the TM are selectively activated by deprivation of an anticipated food under scheduled feeding and functionally innervate the H1R-expressing neurons in the cARC.
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