H3 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing retrieval.
BACKGROUND
Accumulated evidence suggests a role for histamine in cognition and the use of H3 receptor antagonists in the treatment of learning and memory disorders.


OBJECTIVE
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.


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.
Pascoli
Vincent
V
Laboratoire Signalisation Neuronale et Régulations géniques CNRS-UMR7102, Université Pierre et Marie Curie, Paris VI, France. vincent.pascoli@snv.jussieu.fr
Boer-Saccomani
Corinne
C
Hermant
Jean-François
JF
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D018727:Muscarinic Antagonists; D010880:Piperidines; C115705:ciproxifan; D012601:Scopolamine; C052075:thioperamide