The histamine H1-antagonist chlorpheniramine facilitates learning in aged rats

The effect of the histamine H1-receptor antagonist chlorpheniramine on inhibitory avoidance conditioning was investigated in 31-month-old rats, using a one-trial step-through avoidance task. Immediately after the learning trial, old rats were injected intraperitoneally with 5 or 10 mg/kg d-chlorpheniramine. Control groups included vehicle-injected old and adult (4-month-old) rats and a group of aged animals given an injection of 10 mg/kg chlorpheniramine 5 h after the training trial. When tested 24 h after training, aged rats receiving 10 mg/kg chlorpheniramine exhibited longer step-through latencies than vehicle-treated old controls, indicative of superior learning of the task. The hypermnestic effects of 10 mg/kg chlorpheniramine were no longer evident when injection was performed 5 h, rather than immediately after the learning trial, ruling out enduring proactive effects of the treatment on test performance. Furthermore, vehicle-treated old rats showed poorer inhibitory avoidance performance than vehicle-treated adult controls. Thus, the improvement in performance after the 10 mg/kg dose of chlorpheniramine can be interpreted in terms of a compensation of performance deficits in the old rats.