Comparative effects of cycloheximide and puromycin on cerebral protein synthesis and consolidation of memory in mice.

Abstract Cycloheximide was injected intracerebrally in mice in amounts which produced 94–95% inhibition of cerebral protein synthesis in the interval between 5 and 8 h after administration. Such animals learned to escape or avoid shock by choosing the correct limb of a T-maze normally 5 h after injection and had normal retention when tested 3 h later. In contrast, mice injected with puromycin in a dose which inhibited protein synthesis less than cycloheximide, had marked impairment of memory 3 h after training. Addition of cycloheximide to the puromycin solution antagonized its amnesic effect. The puromycin effect on memory 3 h after training is, therefore, probably not based on inhibition of synthesis of a protein required for memory storage. A possible role of protein synthesis in ‘consolidation’ of memory in mice is not supported by these experiments.