Anxiety and cognition in histamine H3 receptor-/- mice

Angela Rizk, Justine Curley, Jennifer Robertson, Jacob Raber

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Histamine H3 receptors (H3Rs) were first characterized as autoreceptors modulating histamine release and synthesis via negative feedback. Acute H3R stimulation or blockade with selective agonists and antagonists suggests a role for H3R in anxiety and cognition. However, little is known about the long-term effects of H3R blockade on brain function. In the current study, mice lacking H3 receptors (H3R-/-) were used to investigate the role of H3R-mediated signalling in anxiety and cognition. H3R-/- mice showed enhanced spatial learning and memory in the Barnes maze. In addition, H3R-/- mice showed reduced measures of anxiety in the elevated plus and zero mazes involving exploratory behaviour and avoidable anxiety-provoking stimuli, but enhanced acoustic startle responses involving unavoidable anxiety-provoking stimuli. These behavioural alterations were associated with higher arginine vasopressin levels in the central and basolateral nuclei of the amygdala. These findings support a role for H3Rs in mediating histamine effects on spatial learning and memory and measures of anxiety.

Original languageEnglish (US)
Pages (from-to)1992-1996
Number of pages5
JournalEuropean Journal of Neuroscience
Issue number7
StatePublished - Apr 2004


  • Acoustic startle response
  • Elevated plus maze
  • Elevated zero maze
  • Spatial learning and memory
  • Vasopressin

ASJC Scopus subject areas

  • Neuroscience(all)


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