Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors

Shinobu Sakurada, Tohru Orito, Seiichi Furuta, Hiroyuki Watanabe, Jalal Izadi Mobarakeh, Kazuhiko Yanai, Takehiko Watanabe, Takumi Sato, Kenji Onodera, Chikai Sakurada, Tsukasa Sakurada

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Intrathecal injection of histamine elicited a behavioral response consisting of scratching, biting and licking in conscious mice. Here, we have examined the involvement of substance P (SP) by using intrathecal injection of tachykinin neurokinin (NK)1 receptor antagonists and SP antiserum. Histamine-induced behavioral response was evoked significantly 5-10 min after intrathecal injection and reached a maximum at 10-15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 200 to 3200 pmol, and maximum effect was observed at 800-1000 pmol. The H1 receptor antagonist, d-chlorpheniramine and pyrilamine but not the H2 receptor antagonists, ranitidine and zolantidine, inhibited histamine-induced behavioral response. The NK1 receptor antagonists, CP-99,994, RP-67580 and sendide, inhibited histamine-induced behavioral response in a dose-dependent manner. A significant antagonistic effect of [D-Phe7, D-His9]SP (6-11), a selective antagonist for SP receptors, was observed against histamine-induced response. The NK2 receptor antagonist, MEN-10376, had no effect on the response elicited by histamine. Pretreatment with SP antiserum resulted in a significant reduction of the response to histamine. No significant reduction of histamine-induced response was detected in mice pretreated with NK A antiserum. The present results suggest that elicitation of scratching, biting and licking behavior induced by intrathecal injection of histamine may be largely mediated by NK1 receptors via H1 receptors in the spinal cord.

Original languageEnglish
Pages (from-to)487-493
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume74
Issue number2
DOIs
Publication statusPublished - 2003 Jan

Keywords

  • Histamine H receptor
  • NK receptor
  • Nociceptive response
  • Substance P

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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