Working memory and impulsivity in the Ts65Dn mouse, a model of Down syndrome

The Ts65Dn mouse is widely considered the best animal model of Down syndrome. These mice display several phenotypic abnormalities that parallel characteristics found in Down syndrome. Although much has been revealed about the phenotype of the Ts65Dn mouse, there remain some aspects of the phenotype of these mice that have yet to be explored. Thus, the current research was conducted as part of a larger effort to characterize the behavioral phenotype of the Ts65Dn mouse. Behavioral characteristics commonly reported to occur more frequently in individuals with Down syndrome include working memory deficits and impulsive behavior. In light of this, the purpose of these studies was twofold: to determine whether aged Ts65Dn mice displayed working memory deficits when compared to age-matched littermate controls (LC), and whether Ts65Dn mice showed higher levels of impulsivity than LC mice. An additional aim of this research was to examine the effects of several pharmacological agents on the above behaviors. For the working memory experiments, the mice were trained under a titrating delayed matching-to-position schedule of reinforcement from 3 months of age to 24 months of age. The results from these lifespan studies indicated that the aged Ts65Dn mouse does not possess a working memory deficit when compared to age-matched controls. Five purported cognitive enhancers were administered throughout these working memory experiments in an attempt to improve memory in these mice. The drugs used for these studies were d-amphetamine, donepezil, memantine, rolipram, and pentylenetetrazole. None of the five drugs improved working memory in either Ts65Dn or LC mice; in fact, d-amphetamine and memantine impaired memory in some of the mice. For the impulsivity experiments, the mice were trained under a fixed-ratio waiting-for-reward schedule of reinforcement from 16 month of age to 20 months of age. The results from the impulsivity experiments indicated that Ts65Dn mice and age-matched LC mice do not differ in level of impulsivity under this particular response inhibition schedule. Two drugs were administered in the impulsivity studies in an attempt to influence impulsive behavior: d-amphetamine and fenfluramine. d-Amphetamine decreased impulsivity, while fenfluramine failed to affect impulsive behavior