Altered behavioral characteristics of sleep-wake cycle and histaminergic systems in histamine H₁ receptor knockout mice

Abstract

Histaminergic neurons play a crucial role in mediating arousal through histamine H₁ receptors (H₁R). To clarify the contribution of H₁R in the control of wakefulness, we characterized the alterations of histaminergic systems and sleep-wake cycle in H₁R knockout (KO) mice. As compared with wild type (WT) mice, H₁R KO mice exhibited 16-20% decreases in the histamine content, the mRNA expressions of histidine decarboxylase (HDC) and histamine H₃ receptor (H₃R), and HDC activity in the hypothalamus. Under the baseline condition, the KO mice showed essentially identical sleep-wake cycles to those of WT mice but with the decreased number of brief awakening (≤16 sec epoch) and the prolonged duration of non-rapid eye movement (NREM) sleep. When ciproxifan, an H₃R antagonist, was given i.p, it increased wakefulness in WT mice but not at all in H₁R KO mice, although the ciproxifan application increased histamine release from the frontal cortex in both genotypes of mice as revealed by in vivo microdialysis. These results indicate that H₁R is important in the regulation of state transitions from NREM sleep to wakefulness and is essential for the arousal effect of an H₃R antagonist. [Jpn J Physiol 55 Suppl:S20 (2005)]