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

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?p?p?1 antagonist, or zolantidine (10 mg/kg), an H₂ antagonist, prevented the retrieval enhancement effect of ciproxifan (p?p?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.