Effects of protein synthesis inhibition on memory for active avoidance training.

Inhibition of brain protein synthesis by anisomycin and acetoxycycloheximide was studied in mice for its biochemical and behavioral effects. By employing both drugs in low doses in a series of injections, we were able to maintain inhibition of protein synthesis of 80% or greater for up to 14 hr without causing detectable permanent physiological impairment. The drugs were employed as amnestic agents in mice trained to avoid footshock in a T-maze. As the duration of inhibition increased, the percentage of mice classed as amnesic increased. This amnesia could be reduced by increasing (a) the rate of acquisition, or (b) the number of training trials. Anisomycin was shown to cause a significant degree of amnesia for the escape component as well as the avoidance component of the learning. A single injection of anisomycin given 15 min prior to training did not cause significant changes in the acquisition or retention of avoidance conditioning, when comparison was made with saline-injected controls. Only additional injections given after training to prolong inhibition caused amnesia. Thus, those injections critical in obtaining amnesia were given at a time at which interference with acquisition could not have occurred, so the results bear clearly on memory processes.