Histamine H3 receptor agonists decrease hypothalamic histamine levels and increase stereotypical biting in mice challenged with methamphetamine

Junichi Kitanaka, Nobue Kitanaka, F. Scott Hall, George R. Uhl, Tomohiro Tatsuta, Yoshio Morita, Koh Ichi Tanaka, Nobuyoshi Nishiyama, Motohiko Takemura

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of the histamine H3 receptor agonists (R)-α- methylhistamine, imetit and immepip on methamphetamine (METH)-induced stereotypical behavior were examined in mice. The administration of METH (10 mg/kg, i.p.) to male ddY mice induced behaviors including persistent locomotion and stereotypical behaviors, which were classified into four categories: Stereotypical head-bobbing (1.9%), circling (1.7%), sniffing (14.3%), and biting (82.1%). Pretreatment with (R)-α-methylhistamine (3 and 10 mg/kg, i.p.) significantly decreasedstereotypical sniffing, but increased stereotypical biting induced by METH, in a dose-dependent manner. This effect of (R)-α-methylhistamine on behavior was mimicked by imetit or immepip (brain-penetrating selective histamine H3 receptor agonists; 10 mg/kg, i.p. for each drug). Hypothalamic histamine levels 1 h after METH challenge were significantly increased in mice pretreated with saline. These increases in histamine levels were significantly decreased by pretreatment with histamine H3 receptor agonists, effects which would appear to underlie the shift from METHinduced stereotypical sniffing to biting.

Original languageEnglish (US)
Pages (from-to)1824-1833
Number of pages10
JournalNeurochemical Research
Volume36
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • Behavior
  • Histamine
  • Hypothalamus
  • Methamphetamine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

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