Actinomycin-D: Effects on Memory at Different Times after Training

Abstract

INHIBITORS of macromolecular synthesis have been used extensively for studies of memory storage. The amnesic effects of two inhibitors of protein synthesis, acetoxy-cycloheximide and cycloheximide, have been attributed to specific interference with the synthesis of protein required for formation of long-term memory^1–4. The effects of actinomycin-D, an inhibitor of DNA-dependent RNA synthesis, have been particularly difficult to interpret because doses sufficient to produce marked inhibition of cerebral RNA synthesis produce fairly rapid onset of irreversible systemic toxicity^5,6. Even much smaller doses produce localized chromatolysis⁷ and may lead to death. Studies with rodents injected before learning show that marked inhibition of RNA synthesis does not interfere with retention for a few hours after injection^5,6,8, but the marked toxicity of this drug has limited its usefulness in studies of the participation of cerebral RNA synthesis in long term memory.