Effects of N-[2-(1-Azabicyclo[3, 3, 0]octan-5-yl)ethyl]2-nitroaniline Fumarate (SK-946), a Novel Cognition Activator, on Learning and Memory in Rodent Models

Abstract

We examined the effects of N-[2-(1-azabicyclo[3, 3, 0] octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) on cognition in various rodent models. SK-946 slightly suppressed spontaneous motor activity, but had no effect on scopolamine-induced motor facilitation. SK-946 ameliorated scopolamine-, pirenzepine-, cycloheximide- and electric shock-induced passive avoidance deficits in rodents when administered before acquiring the training. In an active avoidance test, SK-946 accelerated avoidance acquisition in the later half of training without a marked increase in lever-pressing. In more reliable models of cognitive disorders, i.e. an AF64A intracerebroventricular infusion model using the step-through passive avoidance test, an aged rat model using the step-down passive avoidance test and methylazoxymethanol (MAM)-induced microencephalic rat model using the Morris water maze test, SK-946 ameliorated impaired learning and memory. These results suggest an ability of SK-946 to enhance cognitive functions.