Olfactory discrimination learning is blocked by leupeptin, a thiol protease inhibitor.

Rats were trained on successive two-odor discriminations with the cues randomly located in an 8-arm radial maze. After several days of training using different odor pairs, the thiol protease inhibitor leupeptin was infused into the ventricles and testing continued. Leupeptin caused a pronounced, dose-dependent and reversible deficit in performance in this task. Previous studies have shown that these drug concentrations do not influence spontaneous activity, feeding and drinking, or the acquisition and retention of avoidance conditioning. The results are interpreted as supporting the hypothesis that a calcium-sensitive proteinase is involved in certain forms of memory that require modification of telencephalic circuitries.