Perinatal leupeptin retards subsequent acquisition of a visual discrimination task in chicks.

Recent discoveries that calcium sensitive proteases (calpains) may play an important role in memory led to investigation of the effects of leupeptin, a calpain inhibitor, on learning. Intracerebral injections of either 0.9% saline, 80 micrograms aprotinin, 306 micrograms glutamate, or 8 or 80 micrograms leupeptin were administered to 95 two-day-old chicks. On Day 10 posthatch, animals were then tested on a task requiring discriminations between pebbles and food pellets. Chicks receiving 8 or 80 micrograms leupeptin or 306 micrograms glutamate were found to be deficient in acquiring the task. Aprotinin, a control serine protease inhibitor, did not retard discrimination learning. None of the drugs tested altered body weight or gross visual skills. These results suggest that retardation produced by leupeptin is not due to nonspecific changes in protease activity, visual competency, or growth. The reported results confirm earlier reports of leupeptin-induced memory impairments in rats.