Histaminergic neurons are involved in the orexigenic effect of orexin-A

E. A. Jørgensen, U. Knigge, T. Watanabe, J. Warberg, A. Kjaer*

*Corresponding author for this work
23 Citations (Scopus)


Orexin-A is an orexigenic peptide expressed mainly in the hypothalamus. Orexin-A increases and anti-orexin-A antibodies decrease food intake. However, the exact mechanism by which orexin-A exerts its orexigenic action is not fully elucidated. The histaminergic system is known to play a role in feeding behavior and we hypothesized that it could be involved in the orexigenic effect of orexin-A. To study this, we used histamine knockout animals and pharmacological blockade of the histaminergic system and studied the effect of orexin-A on feeding behavior and gene expression of neuropeptide Y (NPY). Orexin-A was administered intracerebroventricularly and food intake measured in wild-type, histamine H1-receptor knockout or histidine decarboxylase knockout mice. Additionally, we administered orexin-A to wild-type mice with pharmacologically blocked H1-receptors or pharmacologically stimulated autoinhibitory H3-receptors. By quantitative real-time PCR we measured the effect of orexin-A on NPY mRNA expression in wild-type and knockout mice. Orexin-A dose-dependently stimulated food intake when administered to wild-type mice in doses up to 0.03 μg. Orexin-A in a dose of 0.01 μg increased food intake 10-fold in wild-type mice, whereas no increase in food intake was seen in either knockout mice or pharmacologically manipulated mice. Orexin-A increased NPY mRNA 4-fold in wild-type mice, whereas no change was observed in knockout mice. We conclude that the orexigenic effect of orexin-A is dependent on an intact histaminergic neuronal system and seems to involve an H1-receptor mechanism.

Original languageEnglish
Issue number2
Pages (from-to)70-77
Number of pages8
Publication statusPublished - 2005
Externally publishedYes


  • Feeding behavior
  • Histamine
  • Neuropeptide Y
  • Orexins
  • Transgenic mice


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