A role of the histaminergic system for the control of feeding by orexigenic peptides.

A considerable number of neuropeptides are involved in the hypothalamic regulation of feeding behavior. We previously reported that leptin, the ob gene product, expressed its anorectic effect though the histaminergic system via histamine H(1) receptors. However, the interactions among the orexigenic neuropeptides, such as orexin-A, neuropeptide Y (NPY), and ghrelin, and the histaminergic system have not yet been clarified. In this study, we investigated the effect of the neuropeptides on the hypothalamic histamine release in rats, and on food intake and locomotor activity in H(1)-receptor knockout (H1R-KO) mice. Orexin-A increased the histamine release and locomotor activity, but not food intake, suggesting that the histaminergic system participates in arousal rather than feeding by orexin-A. NPY also increased histamine release, but its effect was not immediate. NPY-injected H1R-KO mice consumed more food than the wild-type mice; thus, the histaminergic system may act as a feedback factor downstream of NPY. Ghrelin did not affect histamine release, and it increased food intake, even in H1R-KO mice. Thus, ghrelin expresses its action in a histamine-independent manner.