Effects of Histamine on Circadian Rhythms and Hibernation

Histamine appears to play a role in regulation of sleep and arousal as well as in synchronizing endogenous circadian rhythms with exogenous photic cues. Direct application of histamine to the suprachiasmatic nucleus (SCN), the site of the mammalian circadian pacemaker, phase shifts the circadian rhythm in neural activity. Intraventricular injections of histamine also phase shift circadian rhythms as do micro-injections directed towards the SCN. The magnitude and direction of the phase shifting effects of histamine depend on circadian phase in a manner similar to light. Depletion of brain histamine levels by inhibition of histamine synthesis reduces phase shifts to light. Histamine appears to influence phase shifts to light via a direct modulation of NMDA receptors in the SCN. Increased histamine levels and turnover observed in hibernating animals render it possible that histamine is a key regulator of hibernation. Thus histamine participates in an important link between sleep, circadian rhythms, and hiber...