Discriminable effects of antimuscarinics: dose response and substitution test studies

In a shock escape T-maze task, rats were trained to turn right following one drug treatment and left following a second drug treatment. The specific drug and dose conditions were the only discriminative cues available to the animals. The number of training sessions before criterion performance indicated the discriminability of the two training conditions. Drug vs no drug training showed that discriminability was proportional to dosage for low doses, but was constant over a range of higher doses. Such an asymptote of discriminability was observed with scopolamine, atropine, benactyzine and Ditran (JB 329), and was shown not to result from tolerance. High dose vs low dose discriminations involving scopolamine were learned very slowly if both doses were within the asymptotic range; this indicates that similar discriminable effects were produced by high and low doses. To compare various drugs, substitution tests were administered to trained rats. The four antimuscarinic drugs generally substituted for one another but did not mimic and were not mimicked by drugs in other pharmacological classes. Some exceptions to this pattern were noted. The discriminable effects of scopolamine were partially antagonized by physostigmine. The results indicate that the antimuscarinic drugs share discriminable actions probably produced by their anticholinergic actions. The asymptote of action at high doses appears genuine, possibly reflecting receptor saturation.