Intraventricular infusion of the histamine H1 receptor antagonist chlorpheniramine improves maze performance and has anxiolytic-like effects in aged hybrid Fischer 344×Brown Norway rats

Abstract 

In the present study we analyzed the effect of continuous intraventricular infusion of the histamine H₁ receptor antagonist d-chlorpheniramine on the performance of 32-month-old Fischer 344/Brown Norway F1 hybrid rats in the place version of the Morris water maze and in two different tests of anxiety (open field and black-and-white exploration). Control groups included vehicle-infused old and adult (3-month-old) F1 hybrids. Chronic infusion of chlorpheniramine improved the maze performance of the old rats and reduced fear-related behaviors in the open field and black-and-white box. Furthermore, long-term administration of chlorpheniramine was found to diminish age-related deficits in motor capacities. The findings substantiate that histamine H₁-receptive sites are involved in learning and fear-related processes and indicate that hypomnesia and hyperanxiety seen in the course of brain aging may be based, in part, on hyperactivation of the central histaminergic neuron system. Furthermore, the data contribute to the behavioral characterization of the Fischer 344/Brown Norway F1 hybrid rat in the context of behavioral gerontopharmacology.