Separate Chemical Inhibitors of Long-Term and Short-Term Memory: Contrasting Effects of Cycloheximide, Ouabain and Ethacrynic Acid on Various Learning Tasks in Chickens

Cycloheximide injected into the brains of chickens 10 min before training does not effect their learning of a visual discrimination task, or memory of that task for at least 1 h after training. When tested 24 h later no memory of the training procedure is detectable. In contrast, ouabain injected 10 min before training prevents the expression of learning during training. The block lasts for up to 1 h, but from that time on memory begins to appear. Ouabain does not affect performance when injected just before testing for memory retention 24 h after training. It therefore affects neither the readout of long-term memory nor motivation nor perceptual abilities necessary for performance of the learning task. In birds treated with ouabain, after training on an operant task for heat reward by a procedure requiring a fixed number of reinforcements, memory is absent 20 min later but is well established at 24 h. Cycloheximide blocks long-term memory of this task. Like ouabain, ethacrynic acid, injected into the brain of chickens 10 min before training prevents the expression of learning of visual discrimination. Ethacrynic acid hastens the decline of memory after one-trial passive avoidance learning. It also blocks observational learning. We conclude that ouabain and ethacrynic acid block access to short-term memory, whereas cycloheximide interferes with the registration of long-term memory. Comparing the pharmacology of ethacrynic acid and ouabain their common known actions are on the Na/K fluxes across cell membranes. We suggest that long lasting changes in distribution of these ions in recently active nerve cells may be at the basis of access to memory during and shortly after learning.