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.
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.
Authors: P Blandina; M Giorgetti; L Bartolini; M Cecchi; H Timmerman; R Leurs; G Pepeu; M G Giovannini Journal: Br J Pharmacol Date: 1996-12 Impact factor: 8.739
Authors: X Ligneau; D Perrin; L Landais; J-C Camelin; T P G Calmels; I Berrebi-Bertrand; J-M Lecomte; R Parmentier; C Anaclet; J-S Lin; V Bertaina-Anglade; C Drieu la Rochelle; F d'Aniello; A Rouleau; F Gbahou; J-M Arrang; C R Ganellin; H Stark; W Schunack; J-C Schwartz Journal: J Pharmacol Exp Ther Date: 2006-09-27 Impact factor: 4.030