Acute donepezil treatment does not attenuate the deficit in learning observed in Ts65Dn mice, a model of Down syndrome

Abstract

The Ts65Dn mouse, a model of Down syndrome, displays a deficit in learning when responding under an incremental repeated acquisition (IRA) schedule of milk presentation. This study examined whether acute administration of donepezil prior to testing would attenuate the learning deficit. Adult male, Ts65Dn and littermate control mice were trained to respond under an IRA schedule. When responding stabilized, an acute dose‐response curve was obtained for donepezil (1–5.6 mg/kg, ip). Following saline administration, Ts65Dn mice earned fewer milk presentations, responded at a lower percent accuracy and had a slower rate of responding than littermate controls. Low doses of donepezil ( 1 and 1.8 mg/kg, ip) given one hour prior to testing did not alter performance in any way. A dose of 3 mg/kg decreased the number of reinforcers earned, and the rate of responding in the Ts65Dn mice, but not in the littermate controls. Following 5.6 mg/kg, rate of responding and the number of milk presentations were decreased in Ts65Dn and littermate control mice. The 5.6 mg/kg dose also decreased the percent correct responding in Ts65Dn mice but not that of littermate controls. These results show that acute administration of donepezil does not attenuate the learning deficit in Ts65Dn mice or increase the learning performance of control mice responding under the IRA task. Supported by NIH grant HD047656.