Modifying effects of histamine on circadian rhythms and neuronal excitability.

Histaminergic activity shows a clear circadian rhythm: high levels during the active period (in rodents at night, in monkeys and humans during the day), and low levels during the sleep period. Histamine appears to be necessary for the maintenance of the circadian rhythmicity of the adrenocortical hormone release, locomotor activity and food intake, and the sleep-wakefulness cycle. In addition, a role for histaminergic neurons in the light entrainment is implicated. In phase shift studies, histamine given centrally seems to entrain the activity rhythm in the same way as light impulses and inhibition of histamine synthesis seems to block the entrainment by light. Importantly, histamine participates in the control of arousal and may be implicated in the sleep disturbances in hepatic encephalopathy. Furthermore, evidence suggests a role for histamine in overall neuronal excitability and seizure susceptibility both in animals and humans. Thus, we conclude that histamine may exert modifying effects on circadian rhythmicity and neuronal excitability.