Effect of d ‐amphetamine·SO 4 on learning in Ts65Dn, a murine model of Down syndrome, at 20‐months of age

Abstract

The Ts65Dn mouse is partially trisomic at chromosome 16 resulting in an overexpression of more than 80% of homologues overexpressed in human patients with trisomy 21. Previous research (Behav. Genet. 34: –119, 2004) using an incremental repeated acquisition (IRA) schedule of reinforcement has shown a significant learning impairment in young adult Ts65Dn (TS) mice compared to littermate controls (LC). The purpose of this study was to examine the effect of d-amphetamine·SO4 (AMP) on learning in TS mice at 20-months of age, under an IRA schedule of reinforcement. Under this schedule, the mouse was required to produce a one-response chain to receive the first 5 milk presentations, a two-response chain to obtain the next 10 milk presentations, a three-response chain for the next 30 milk presentations, and a four-response chain for the final 20 milk presentations. Although the dose of AMP producing the maximum benefit was quite variable across subjects, following the administration of 0.1, 0.3, 1.0, or 3.0 mg/kg of AMP, 75% of the 20–month old Ts65Dn mice earned more milk presentations then when given saline. The same doses failed to produce a significant increase in the number of milk presentations earned by LC mice. These data indicate that AMP-like drugs may be beneficial to some older patients with Down syndrome. Supported in part by funds NIH grant HD047656 (G.R.W.) and the NIEHS pre-doctoral training grant 5T32ES01952.