Neither donepezil nor d‐amphetamine improve working memory in the Ts65Dn mouse, a murine model of Down syndrome

Abstract

The Ts65Dn mouse, a model of Down syndrome, has a partial trisomy of chromosome 16. Previous research using an incremental repeated acquisition schedule of reinforcement has shown that there is a significant learning impairment in Ts65Dn mice compared to littermate controls (LC) (Wenger et al. Behav. Genet. 34: 105–119, 2004). The purpose of this study was to examine the effect of d‐amphetamine (0.1 – 10 mg/kg) and donepezil (0.3 – 5.6 mg/kg) on working memory in young adult, male Ts65Dn and LC mice responding under a titrating, delayed matching‐to‐position schedule of reinforcement. When the behavior stabilized, the length of the mean delay for the session achieved by the two lines of mice was indistinguishable, but rates of responding engendered by the sample stimulus were higher in the LC mice than in the Ts65Dn mice. Low to moderate doses of donepezil and d‐amphetamine failed to alter the rate of responding or the length of the mean delay for the session. However, significant decreases in the rate of responding and the mean delay length were observed at high doses of both drugs. These results show that the acute administration of these agents is ineffective in improving working memory in either the young adult Ts65Dn mice or age‐matched LC mice. Future studies will evaluate the efficacy of these agents as the animals age and following chronic administration. Supported by NIH grant HD047656 (G.R.W.)