Effects of thioperamide, a histamine H3 receptor antagonist, on locomotor activity and brain histamine content in mast cell-deficient W/Wv mice

Naruhiko Sakai, Kenji Onodera, Kazutaka Maeyama, Kazuhiko Yanai, Takehiko Watanabe

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Abstract

The purpose of this study was to examine the effects of thioperamide, a histamine H3 antagonist, on the locomotor activity and the brain histamine content in mastcell- deficient W/Wv mice. Thioperamide (12.5 and 25 mg/kg) showed significant increase in the locomotor activity of W/Wv mice, measured by a photobeam system, 1 hr after the intraperitoneal injection. However, more than 75 mg/kg of thioperamide showed not only the reduction of the locomotor activity but also the inhibition of motor coordination measured by the rotarod performance. The increase in the locomotor activity by thioperamide was blocked by i. p. pretreatment with (R) - α -methylhistamine, an H3 agonist, or pyrilamine, an H1 antagonist, or zolantidine, an H2 antagonist. The brain histamine content was decreased by thioperamide (12.5-75.0 mg/kg), 1 hr after administration. Thus, the blockade of histamine H3 receptor by thioperamide showed the activation of locomotor activity of mice, which may be mediated by H1 and/or H2 receptors. The present data support the hypothesis that central histaminergic neurons may be involved in the control of state of wakefullness.

Original languageEnglish
Pages (from-to)2397-2404
Number of pages8
JournalLife Sciences
Volume48
Issue number25
DOIs
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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