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H3 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing retrieval.

AbstractRATIONALE:
Accumulated evidence suggests a role for histamine in cognition and the use of H3 receptor antagonists in the treatment of learning and memory disorders.
OBJECTIVES:
The aim of the current study was to investigate the cognition enhancing properties of ciproxifan, an H3 receptor antagonist, after natural forgetting in normal adult rats.
MATERIALS AND METHODS:
The novel object discrimination task, a recognition memory test based on spontaneous exploratory behaviour, was used. Briefly, rats exposed to two identical objects during an acquisition trial can discriminate between a novel object and a familiar one during a subsequent choice trial after a short delay but not after a 24-h inter-trial interval.
RESULTS:
The scopolamine (0.5 mg/kg, i.p.)-induced impairment after a short delay was abolished by ciproxifan (p < 0.001). Natural forgetting was prevented by a single administration of ciproxifan (3 mg/kg) prior to the retention test (p < 0.001) but not when administered before or immediately after the acquisition trial (schedule effect p < 0.05), demonstrating a specific activity on memory retrieval. Pretreatment with either pyrilamine (10 mg/kg), an H1 antagonist, or zolantidine (10 mg/kg), an H2 antagonist, prevented the retrieval enhancement effect of ciproxifan (p < 0.05 and p < 0.001, respectively).
CONCLUSIONS:
Histamine H3 receptor antagonists restore the performance of rats impaired by scopolamine and enhance recognition memory after acute administration before the retrieval phase via a mechanism dependent on H1 and H2 receptor activation.
AuthorsVincent Pascoli, Corinne Boer-Saccomani, Jean-François Hermant
JournalPsychopharmacology (Psychopharmacology (Berl)) Vol. 202 Issue 1-3 Pg. 141-52 (Jan 2009) ISSN: 1432-2072 [Electronic] Germany
PMID18493749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Histamine H1 Antagonists
  • Histamine H2 Antagonists
  • Histamine H3 Antagonists
  • Imidazoles
  • Muscarinic Antagonists
  • Piperidines
  • ciproxifan
  • Scopolamine
  • thioperamide
Topics
  • Animals
  • Discrimination Learning (drug effects)
  • Discrimination, Psychological (drug effects)
  • Exploratory Behavior (drug effects)
  • Histamine H1 Antagonists (pharmacology)
  • Histamine H2 Antagonists (pharmacology)
  • Histamine H3 Antagonists (pharmacology)
  • Histamine Release (drug effects)
  • Imidazoles (pharmacology)
  • Male
  • Memory (drug effects)
  • Mental Recall (drug effects)
  • Muscarinic Antagonists (pharmacology)
  • Piperidines (pharmacology)
  • Psychomotor Performance (drug effects)
  • Rats
  • Rats, Wistar
  • Recognition, Psychology (drug effects)
  • Scopolamine (antagonists & inhibitors, pharmacology)

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