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Classical conditioning of the nictitating membrane-eyeblink response in young (7 months old) and older (36 months old) New Zealand white rabbits in a delay paradigm with a 400-ms conditioned stimulus-unconditioned stimulus interval was examined for initial acquisition and retention. Older animals required significantly more acquisition trials to reach learning criterion. Age differences in acquisition were temporary. Older rabbits responded at a level comparable to that of young rabbits such that total performance over the 630 trials of acquisition was not different. Rabbits in the explicitly unpaired control groups exhibited no age differences in unconditioned response amplitude or latency measures. Twelve- and 18-month retests demonstrated no significant age effects on retention. Patterns of retention differed between the age groups. Older rabbits required fewer trials to obtain the learning criterion at each phase of testing. Younger rabbits maintained a stable performance throughout training.

BMY 21502, a substituted pyrrolidionone, has been found to enhance a simple form of learning in older rabbits. In humans, this simple type of learning, classical conditioning of the eyeblink response, declines in normal aging and is seriously impaired in Alzheimer's disease (AD). We have demonstrated that eyeblink classical conditioning reliably discriminates patients diagnosed with probable AD from non-demented, age-matched elderly subjects. Older organisms can be classically conditioned, but they condition at a much slower rate than younger organisms. Our preliminary analyses indicate age differences in distribution of protein kinase C in the hippocampus. Here we also report that older rabbits that are administered two different doses of BMY 21502 classically condition at a rate approximating that of young rabbits.

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