Memory enhancement: supra-additive effect of subcutaneous cholinergic drug combinations in mice.
The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent treatment strategy is to combine present drugs to improve their memory enhancing effect. We used mice weakly trained on active avoidance in a T-maze to compare the effect of cholinergic drugs, given alone and in two-drug combinations, on retention test performance. All drugs were injected SC immediately after training. Memory retention was tested 1 week later. A dose-response curve was determined for each of four drugs (arecoline, edrophonium, oxotremorine, tacrine) and for each of the six possible two-drug combinations. 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 (66.2%-95.7%) in the optimal dose for enhanced retention was observed with these two-drug combinations.
D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D004357:Drug Synergism; D004491:Edrophonium / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology
D010277:Parasympathomimetics; D001115:Arecoline; D013619:Tacrine; D010095:Oxotremorine; D004491:Edrophonium