Differential effects of scopolamine on working and reference memory depend upon level of training.

Controversy exists whether the cholinergic system in the brain is involved in working memory (WM) selectively or in both WM and reference memory (RM). Rats were trained to obtain food from four baited arms of an eight-arm radial maze. The remaining arms were never baited. Three types of errors were recorded: entry into unbaited arms (RM errors), reentry into baited arms (WM errors), and reentry into unbaited arms (WRM errors). There were no differences among three control conditions: methyl scopolamine, physiological saline, and uninjected. Scopolamine increased WM but not RM errors. When rats were trained to a higher criterion of learning, however, both WM and RM were impaired. It appears that when baseline error rate is sufficiently low RM errors under scopolamine become observable. The results suggest that the cholinergic system is involved in both WM and RM, and the selective involvement of WM is the result of insufficient training. The controversy in the literature over the involvement of the cholinergic system in WM and RM was addressed.