Age-related cognitive impairments as assessed with an automated repeated measures memory task: implications for the possible role of acetylcholine and norepinephrine in memory dysfunction.

Although there exists a general agreement that certain aspects of learning and memory, and certain associated neuronal systems may be impaired with aging, systematic parametric studies are needed to characterize the nature and limits of these age-related impairments and to identify the underlying neuronal mechanisms. We review a series of experiments that examined the effects of aging and experimental treatments on rats' performance of a continuous nonmatching-to-sample, working memory task. In these studies, disruption of cholinergic transmission produced robust impairments that increased with retention interval duration, but could be observed even at the shortest intervals tested. In contrast, age-related impairments were less robust. With tone and light discriminative stimuli age-related impairments were not observed under conditions that were sensitive to disruption of cholinergic transmission, but were observed with increased retention interval duration. Finally, disruption of noradrenergic transmission produced a marginal disruption of memory performance, at worst. The generality of these results, and possible implication for future studies and animal models of dementia are discussed.