H3 receptor antagonists reverse delay-dependent deficits in novel object discrimination by enhancing retrieval
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- Pascoli, V., Boer-Saccomani, C. & Hermant, JF. Psychopharmacology (2009) 202: 141. doi:10.1007/s00213-008-1171-2
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Accumulated evidence suggests a role for histamine in cognition and the use of H3 receptor antagonists in the treatment of learning and memory disorders.
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.
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).
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.