Effect of Acetoxycycloheximide on Learning and Memory of a Light–Dark Discrimination

Abstract

THERE are reasons to believe that memory storage, particularly “long-term” memory storage, is mediated by the synthesis of protein which facilitates synaptic connexions¹. We have recently reported studies which show that cerebral protein synthesis may be necessary for “long-term” memory but not for learning or “short-term” memory². In these studies mice whose cerebral protein synthesis at the time of training had been inhibited about 95 per cent by intracerebral injections of acetoxycycloheximide were found to learn a left–right discrimination in a T maze normally, to remember normally 3 h after training, but to have marked impairment of memory 6 h or more after training. The effect of acetoxycycloheximide on memory 6 h or more after training (“long-term” memory) was marked when training was continued until the mice made three out of four consecutive correct responses, but was not significant when training was continued until the mice made nine out of ten consecutive correct responses. We concluded from these findings that the small amount of intact protein synthesizing capacity might be sufficient to mediate storage of memory if repeated training of a very simple task was given. It therefore seemed worthwhile to determine the effects of acetoxycycloheximide on learning and memory of a more difficult task. This report describes the effects of this drug on learning and memory of a light–dark discrimination in a T maze. We found, as in our studies with the left–right discrimination, that acetoxycycloheximide had no effect on learning or on memory of the correct solution for 3 h after learning, but it did impair memory 6 h or more after learning. With this task the effect of acetoxycycloheximide was striking even when training was continued to a criterion of nine out of ten consecutive correct responses.