Mice were trained in step-down passive avoidance behavior. Bitemporal
injections of
puromycin (PM) were given either immediately or delayed until 24 hrs after training. PM produced a marked
amnesia in both cases during retention testing 3 days later. The
amnesia persisted during a second retention test 6 days after training. Of all the
antibiotics, only PM is effective as an amnestic agent when
injections are delayed 24 or more hours after training.
cycloheximide (CXM) was also injected bitemporally immediately after training. However, CXM produced a weaker amnestic effect even though it produced a much greater inhibition of cerebral
protein synthesis, more rapidly, and of longer duration. In an effort to attenuate the
amnesia produced by PM, in separate experiments, the mice were injected with combined
injections of PM and and CXM (bitemporally): mice were also given combined
injections of PM (bitemporally) and
amphetamine (subcutaneously). The
amnesia produced by immediate
injections of PM wa not attenuated by either CXM or
amphetamine. However, the
amnesia produced by delayed
injections of PM was attenuated by both CXM and
amphetamine. These results suggest that delayed
injections of PM (25 hours after training) block the expression or retrieval of memory. This study also supports the contention that
puromycin has two separate effects on memory with different temporal parameters depending on when the
drug is injected relative to initial training.