Distinctive role of central histamine H3 receptor in various orexigenic pathways.

Despite the well-established role of histamine as an anorexigenic neurotransmitter, the role of histamine H3 receptors in feeding behavior is controversial. Herein we investigated the role of histamine H3 receptor on several orexigenic agents in mice. Thioperamide (histamine H3 receptor inverse agonist) inhibited neuropeptide Y- and nociceptin-induced hyperphagia but had no effect on U-50488 (opioid κ-receptor agonist)-induced hyperphagia. In contrast, imetit (histamine H3 receptor agonist) inhibited U-50488-induced hyperphagia but augmented neuropeptide Y-induced hyperphagia while it did not alter nociceptin-induced hyperphagia. These results indicate distinctive roles of histamine H3 receptors in various orexigenic pathways.