Memory retention: potentiation of cholinergic drug combinations in mice

The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent strategy is to combine present drugs, to improve their memory enhancing effect. We utilize mice weakly trained on active avoidance in a T-maze in order to compare the effect on retention test performance of cholinergic drugs given alone and in two-drug and three-drug combinations. All drugs were injected intraventricularly immediately after training. Memory retention was tested one week later. A dose-response curve was determined for each of four drugs (arecoline, edrophonium, oxotremorine, deanol) and for several of their fixed-ratio combinations. The results indicate that each drug and each combination improved retention test performance up to an optimal dose; the improvement decreased with further increases in dose. A striking reduction (as much as 95%) in the optimal dose for enhanced retention was observed with these two-drug combinations, and further reduction with a three-drug combination. The practical implications of planned drug interactions as an improved means of treating amnesias associated with aging are under investigation.