Effect of histamine depletion on the circadian amplitude of the sleep-wakefulness cycle.

Behavioral states of rats were automatically classified with a newly developed computer program into three sleep stages (awake, slow-wave sleep and REM sleep) from continuous long-term EEG and EMG recordings for several circadian cycles under entrained circumstances (L:D = 12:12). Histamine was depleted by 100 mg/kg intraperitoneal administration of a specific inhibitor of its synthesis, alpha-fluoromethylhistidine, in the mid-light period. This treatment had no effect on the amount of each sleep stage in the total 24-h period or in the light period, but caused significant increases in slow-wave sleep and REM sleep in the dark period. Equivalent decrease in the awake stage during the dark period was also observed. As a result, histamine depletion decreased the light:dark ratio of slow-wave sleep. These findings suggest that decrease of the histamine content of the brain attenuated the circadian amplitude of sleep-wakefulness by suppressing the surge of wakefulness during the dark period. From these results, histamine is suggested to modulate the circadian amplitude of the sleep-wakefulness cycle.