HYPOTHALAMIC NEURONAL HISTAMINE REGULATES FEEDING CIRCADIAN-RHYTHM INRATS

To clarify involvement of hypothalamic neuronal histamine in feeding c ircadian rhythm, we analyzed rat behavioral patterns using chemical pr obes which affect endogenous histaminergic activity. Sustained infusio n of alpha-fluoromethylhistidine (FMH), a specific suicide inhibitor o f a histamine-synthesizing enzyme, into the rat third cerebral ventric le disrupted light-dark cycles of feeding, drinking, and ambulatory be havior. Food and water intake and ambulatory activity during the 12-h light period increased, and those during the 12-h dark period decrease d 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 decrease d in all behavioral parameters, whereas only the acrophase of ambulato ry activity shifted forward after FMH infusion. Chlorpheniramine, an H -1-antagonist. selectively increased food intake during the light and decreased it during the dark period. Consequently, the antagonist incr eased the L/T ratio in food intake, but did not affect the ratio in wa ter intake or ambulatory activity. Famotidine, an H-2-antagonist, did not affect the ratio in any parameter. Thioperamide, an antagonist of auto-inhibitory effects on histamine synthesis and release at presynap tic H-3-receptor sites, decreased food intake during the dark, but did not affect the L/T ratio in any parameter. These findings indicate th at neuronal histamine may regulate feeding circadian rhythm through th e hypothalamic histamine H-1-receptor in rats.