Oral tacrine administration in middle-aged monkeys: effects on discrimination learning.

We studied the effect of chronic, oral administration of 1,2,3,4 tetrahydro-9-aminoacridine (THA), an anticholinesterase, on the acquisition of a color discrimination task in five monkeys (Macaca radiata), aged 13-19 years. A two-phase experiment was performed: initially, one animal was used and served as his own control in a multiple dose, crossover, placebo controlled trial, designed to establish a dose-response curve and an optimal dose range based on THA serum concentrations. Thereafter, four monkeys were given the optimal dose of THA (5.0 mg/day) determined previously while learning up to four color pair discriminations. They also learned up to four other color pair discriminations while on placebo. Two monkeys received THA first, then placebo; the others received placebo first, then THA. No order effects were noted. When combined scores for THA tests were compared to their placebo scores, the difference was significant at p less than 0.01 with all four THA treated monkeys requiring fewer trials to reach learning criterion. These results indicate that THA has a significantly positive effect on the acquisition of a color discrimination task.