抄録
Continuous wakefulness increases demands of sleep, and thus arousal-inducing network and sleep-inducing network should be reciprocally interacted. Histamine has been described as one of neurotransmitters controlling arousal. This hypothesis is in agreement with sleepiness caused by classical anti-histamine drugs, whereas neuronal mechanisms involved are not fully understood. The tuberomamillary nucleus of posterior hypothalamus contains cell bodies of histaminergic neurons. These neurons are tonically active during wakefulness but cease firing during sleep. It has also shown that histaminergic axons are dense in the medial preoptic area (MPOA) and extracellular histamine concentrations in the MPOA couple to arousal states. Our studies also demonstrated that in vivo recordings of action potential firings in the MPOA couple to arousal states in rats. Since preoptic area has been proposed as critical centers for non-REM sleep regulations, we further analyzed distribution of functional histamine receptors using organotypic cultures of mouse MPOA by Ca2+ imaging techniques. The results demonstrated that histamine evoked Ca2+ transient in MPOA neurons but not in the ventrolateral preoptic nucleus neurons. The Ca2+ response in MPOA neurons was resistant to tetrodotoxin but was completely inhibited by the H1 histamine blocker, chlorpheniramine. Since chlorpheniramine has hypnotic effects in vivo, these results suggest arousal signal-feedback to the preoptic sleep centers via histaminergic systems. [J Physiol Sci. 2008;58 Suppl:S91]
