Converging lines of research have implicated a causal relationship between oligomers of amyloid-β and the cognitive impairments associated with Alzheimer's disease (AD); however, very few studies have provided direct experimental evidence of this relationship and none of those studies have used an established model of working memory. The present study used an established model of working memory, the radial-arm maze, to examine the effects of amyloid-β oligomers on the memory of two groups of rats. The experimental group received ICV injections of the culture media (CM) of Chinese Hamster Ovary (CHO) cells transfected with a human mutation of APP containing concentrations of soluble amyloid-β oligomers, which are thought to cause early onset AD (i.e., 7PA2 CM). The control group received similar IVC injections which had not been transfected with APP and did not contain these oligomers (i.e., CHO-CM). The 7PA2 CM significantly disrupted working memory, but the CHO-CM had no effect on memory. The disruptive effects of 7PA2 were evident two hours after exposure and disappeared within a day. These findings confirm the disruptive effects of 7PA2 CM and extend them to a widely accepted model of spatial memory in rodents.