Alpha-fluoromethylhistidine, a histamine synthesis inhibitor, inhibits orexin-induced wakefulness in rats

Seki Yasuko, Akanmu Moses Atanda, Matsuura Masato, Yanai Kazuhiko, Honda Kazuki

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Orexins A and B are involved in the regulation of feeding and arousal state. Previously, we reported that third intracerebroventricular (icv) infusion of both orexins A and B induced a significant arousal effect in rats. We determined the effects of intraperitoneal (i.p.) injection of alpha-fluoromethylhistidine (α-FMH), a histamine synthesis inhibitor, on orexin-induced wakefulness in freely behaving rats. Male Sprague-Dawley rats were chronically implanted with cortical electroencephalogram (EEG) and neck electromyogram (EMG) electrodes, and a cannula for icv infusion. EEG and EMG were monitored for three consecutive days during continuous icv saline infusion at a rate of 10 μl/h. For a 5-h diurnal period, orexin-B (10 nmol/50 μl saline) replaced the icv infusion of saline. α-FMH (100 mg/kg, i.p.) was administered 6 h before icv infusion of orexin-B. Orexin-B at a dose of 10 nmol/h markedly increased the amount of wakefulness by 99.4% (p < 0.05) over the baseline value, whereas α-FMH decreased orexin-B-induced wakefulness by 48.8%. Orexin-B-induced suppression of non-REM sleep was reversed by α-FMH treatment. Pretreatment with α-FMH, significantly inhibited orexin-B-induced wakefulness in rats. The findings of this study therefore suggest that arousal-state regulation by orexin neurons is possibly mediated via the histaminergic system in the tuberomammilary nucleus.

Original languageEnglish
Pages (from-to)151-154
Number of pages4
JournalBehavioural Brain Research
Volume207
Issue number1
DOIs
Publication statusPublished - 2010 Feb 11

Keywords

  • Histamine
  • NREM sleep
  • Orexin
  • REM sleep
  • Rats
  • Wake
  • α-FMH

ASJC Scopus subject areas

  • Behavioral Neuroscience

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