Temporal and pharmacological parameters of puromycin-induced amnesia.

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.