Trialwise tracking method for measuring drug-affected sensory threshold changes in animals.

Rats and rhesus monkeys were trained under a multiple schedule, the components of which were random ratio schedules for food presentation and for shock presentation. The discriminative stimulus for the shock presentation component was a pure tone for the rats and a light for the rhesus monkeys. In the test session under the extinction condition for the shock presentation component, the intensity of the discriminative stimulus was successively either decreased by fixed units when the conditioned suppression was observed or increased when the conditioned suppression was not observed. The levels finally oscillated within a narrow range around the threshold. The auditory thresholds of rats were increased by intramuscular administration of quinidine at 20 mg/kg and also by repeated intramuscular administration of kanamycin at 250 and 500 mg/kg/day. In rhesus monkeys, visual thresholds were raised by application of pilocarpine at 0.02-0.16 mg/kg to the eyes and also by subcutaneous administration of LSD-25 at 4-8 micrograms/kg in one monkey and at 20-30 micrograms/kg in another. The method used for tracking the animals' sensory thresholds was sensitive enough to test the selective effect of the drugs and was also a relatively easy way to obtain a stable behavioral baseline for experimental purposes.