Hypothalamic neuronal histamine regulates feeding circadian rhythm in rats

To clarify involvement of hypothalamic neuronal histamine in feeding circadian rhythm, we analyzed rat behavioral patterns using chemical probes which affect endogenous histaminergic activity. Sustained infusion of alpha-fluoromethylhistidine (FMH), a specific suicide inhibitor of a histamine-synthesizing enzyme, into the rat third cerebral ventricle disrupted light-dark cycles of feeding, drinking, and ambulatory behavior. Food and water intake and ambulatory activity during the 12-h light period increased, and those during the 12-h dark period decreased after the infusion. The ratio of the light period to the 24-h total period (L/T ratio) increased in all behavioral parameters. Assessed by 3-h cumulative analysis, amplitudes of circadian rhythmicity decreased in all behavioral parameters, whereas only the acrophase of ambulatory activity shifted forward after FMH infusion. Chlorpheniramine, an H1-antagonist, selectively increased food intake during the light and decreased it during the dark period. Consequently, the antagonist increased the L/T ratio in food intake, but did not affect the ratio in water intake or ambulatory activity. Famotidine, an H2-antagonist, did not affect the ratio in any parameter. Thioperamide, an antagonist of auto-inhibitory effects on histamine synthesis and release at presynaptic H3-receptor sites, decreased food intake during the dark, but did not affect the L/T ratio in any parameter. These findings indicate that neuronal histamine may regulate feeding circadian rhythm through the hypothalamic histamine H1-receptor in rats.