Effect of d‐amphetamine on learning in the Ts65Dn, 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 (IRA) 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 on learning impairments in Ts65Dn and LC mice under an IRA schedule of reinforcement. For the first 5 milk presentations under the IRA schedule the mouse was required to make a one-response chain, completion of a two-response chain was required for the next 10 milk presentations, completion of a three-response chain produced each of the next 30 milk presentations, and finally completion of a four-response chain produced each of the final 20 milk presentations. Following saline LC mice performed at a higher level of accuracy and earned more milk presentations than Ts65Dn mice. d-Amphetamine doses of 0.1, 0.3, or 1.0 mg/kg failed to improve the acquisition performance of LC mice. In contrast, Ts65Dn mice given the same doses responded at a higher level of accuracy and earned more milk presentations than that observed following saline. Thus, following low to moderate doses of d-amphetamine, the performance of Ts65Dn and LC mice was similar. This data indicates that amphetamine-like drugs may be beneficial to patients with Down syndrome. Supported by NIH grant HD047656 (G.R.W.) and NIEHS pre-doctoral training grant 5T32ES01952.