Brain protein synthesis and memory: the use of antibiotic probes

The interest in antibiotics as amnestic agents stemmed from their effects on protein synthesis. Initially they were viewed as an avenue for exploring various hypotheses concerning the role of protein synthesis in memory formation. Three classes of protein synthesis inhibitors have been widely used in memory-disruption experiments: puromycin (Puro), the glutarimides such as cycloheximide (CXM) and acetoxycycloheximide, and, more recently, anisomycin (ANI). Each of these agents has been found effective in producing experimental amnesia within dose ranges that are not significantly toxic to the animal. Although a factor common to each is the ability to block protein synthesis, the biochemical mechanisms for protein synthesis inhibition differ for these drugs in a consequential manner. Each of these agents may have other biochemical effects as well. In fact, it appears that protein synthesis inhibition is not a crucial factor underlying their behavioral effects. For example, data from experiments with CXM and ANI suggest that protein synthesis may not be essential for the storage of longer-term memory in mammals, birds, or insects. Even when retention deficits are produced by protein synthesis inhibition, the effects appear to result from deficits in retrieval or access processes rather than in the storage of memory. Puro, on the other hand, appears to exert its effects on memory in a unique manner. Of all the antibiotics, it alone is effective in producing amnesia when injections are delayed until 24 h after training.