The histamine H₃-receptor inverse agonist pitolisant improves fear memory in mice.

Abstract

Numerous studies have demonstrated that brain histamine plays a crucial role in learning and memory and histamine H3 receptor inverse agonists (H3R inverse agonists) have been proposed to treat cognitive disorders. Pitolisant (BF2.649, 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine, hydrochloride) was the first H3R inverse agonist that has been tested in human trials and is well tolerated. The present study investigated whether Pitolisant (0.625-20mg/kg, i.p.) improves consolidation and reconsolidation processes in the fear conditioning task in female C57BL/6J mice. We also tested whether Pitolisant reverses memory deficits induced by the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (MK-801). Our results indicate that post-training systemic injections of Pitolisant facilitated consolidation of contextual fear memory and reversed amnesia induced by an i.p. injection of 0.12 mg/kg dizocilpine. In addition, none of the doses of Pitolisant we have tested after reactivation (reexposure to the context in which training took place 48 h earlier) affected reconsolidation, whereas dizocilpine disrupted it. However, Pitolisant was able to reverse the deficit in reconsolidation induced by 0.12 mg/kg dizocilpine. The present results are the first demonstration that Pitolisant is effective in improving consolidation processes in the fear condition task and add further evidence to its potential for treating cognitive disorders.

• Authors: Christian Brabant, Yana Charlier, Ezio Tirelli
• Journal: Behavioural brain research (Behav Brain Res) Vol. 243 Pg. 199-204 (Apr 15 2013) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 23327739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Excitatory Amino Acid Antagonists
• Histamine Agonists
• Piperidines
• pitolisant
• N-Methylaspartate
• Dizocilpine Maleate

Topics

• Animals
• Behavior, Animal (drug effects)
• Dizocilpine Maleate (administration & dosage, pharmacology)
• Excitatory Amino Acid Antagonists (administration & dosage, pharmacology)
• Fear (physiology)
• Female
• Histamine Agonists (administration & dosage, pharmacology)
• Memory (drug effects)
• Mice
• Mice, Inbred C57BL
• N-Methylaspartate (antagonists & inhibitors)
• Piperidines (administration & dosage, pharmacology)