Differential effects of scopolamine and lorazepam on working memory maintenance versus manipulation processes

Between-study comparisons of benzodiazepine and anticholinergic drugs on working memory suggest that anticholinergics may produce greater impairment in maintenance processes, whereas benzodiazepines may produce greater impairment in manipulation processes. This study directly compared acute effects of the benzodiazepine lorazepam (1.0 and 2.0 mg/70 kg, orally administered) and the anticholinergic scopolamine (0.25 and 0.50 mg/ 70 kg, subcutaneously administered) on working memory maintenance (storage and rehearsal) and manipulation processes in a placebo-controlled, double-dummy, double-blind, crossover design in 20 healthy volunteers. Using a modified Sternberg paradigm, storage, rehearsal, and manipulation processes were parametrically manipulated by varying memory load, delay between stimulus presentation and test, and number of operations performed on the letter strings, respectively, while controlling for drug effects on nonmemory processes. As predicted, the results suggested greater impairment in maintenance processes (rehearsal) with scopolamine than with lorazepam and greater impairment in manipulation processes with lorazepam than with scopolamine. In addition, the results suggested greater overall slowing of working memory processes with lorazepam.