Effects of the cholinesterase inhibitors donepezil and metrifonate on scopolamine-induced impairments in the spatial cone field orientation task in rats

Abstract

The aim of these experiments was to assess whether the clinically validated cognition enhancers donepezil (Aricept™, E2020) and metrifonate antagonize scopolamine-induced deficits in the cone field, a complex spatial discrimination task. The cone field task allows measurement of the effects of experimental manipulations on working and reference memory (WM and RM), search strategies, and on the speed and latency to execute the task. The effects of a single administration of donepezil (0.1, 0.3, and 1.0 mg kg −1, p.o.) and metrifonate (30, 60, and 120 mg kg −1, p.o.) were investigated in adult Harlan–Wistar rats trained to a stable level of performance and pretreated with scopolamine (0.5 mg kg −1, i.p. 30 min before training). Scopolamine impaired WM without inducing overt non-cognitive side-effects. Donepezil did not antagonize the scopolamine-induced deficits, whereas metrifonate antagonized the WM deficits at the dose of 60 mg kg −1, but not at 30 or 120 mg kg −1. Thus, a cholinesterase inhibitor with proven clinical efficacy can antagonize scopolamine-induced spatial memory deficits. The cone field would be a useful component of a behavioral screening battery to test the effects of putative cognition enhancers.