Hypothalamic Neuronal Histamine Modulates Adaptive Behavior and Thermogenesis in Response to Endogenous Pyrogen

Abstract

Homeostatic involvement of hypothalamic neuronal histamine in adaptive behavior and thermogenesis was investigated when interleukin‐1β (IL‐1β), one of the endogenous pyrogens, was infused peripherally in rats. IL‐1β decreased food and water intake and elevated body temperature. Depletion of neuronal histamine in the hypothalamus induced by α‐fluoromethylhistidine, a suicide inhibitor of the histamine synthesizing enzyme histidine decarboxylase (HDC), attenuated the suppressive effect of IL‐1β on food intake, facilitated the inhibitory effect on water intake, and enhanced its thermogenic effect. Simultaneously IL‐1β increased activity of HDC and histamine‐N‐methyltransferase (HMT), a neuronal histamine catabolizing enzyme. Pretreatment with indomethacin completely blocked those increases in turnover of neuronal histamine induced by IL‐1β. Hypothalamic prostaglandin E2 (PGE2) activated by peripheral IL‐1β, but not peripheral PGE2, increased both activities of HDC and HMT. Ginsenoside Rg1 a major component of panax ginseng, modulated the suppressive effects of IL‐1β on ingestive behavior, resulting in a lowering of body temperature. The findings suggest that the effects of IL‐1β on ingestive behavior and thermogenesis may be modulated by dynamics of hypothalamic neuronal histamine through activation of hypothalamic PGE2 which is elevated by peripheral IL‐1β. 1995 North American Association for the Study of Obesity (NAASO)