Psychopharmacology

, Volume 202, Issue 1, pp 141–152

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

  • Vincent Pascoli
  • Corinne Boer-Saccomani
  • Jean-François Hermant
Original Investigation

DOI: 10.1007/s00213-008-1171-2

Cite this article as:
Pascoli, V., Boer-Saccomani, C. & Hermant, JF. Psychopharmacology (2009) 202: 141. doi:10.1007/s00213-008-1171-2

Abstract

Rationale

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.

Keywords

Histamine H3 receptorCiproxifanThioperamideNovel object discrimination (NOD) testMemory-retrieval processes

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Vincent Pascoli
    • 1
    • 3
  • Corinne Boer-Saccomani
    • 2
  • Jean-François Hermant
    • 2
  1. 1.Laboratoire Signalisation Neuronale et Régulations géniques CNRS-UMR7102Université Pierre et Marie CurieParis VIFrance
  2. 2.Pharmacologie du Système Nerveux CentralCentre de Recherches de CephalonMaisons-AlfortFrance
  3. 3.ParisFrance