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Male Swiss albino CD-1 mice given a single subcutaneous injection of a cerebral protein synthesis inhibitor, anisomycin (ANI; 1 mg/animal), 20 min prior to a single trial of passive avoidance training demonstrated impaired retention at tests given 3 hr, 6 hr, 1 day, and 7 days after training. Retention was not significantly different from that of saline controls when tests were given .5 or 1.5 hr after training. Prolonging inhibition of brain protein synthesis by giving either one or two additional injections of ANI at 2 hr or at 2 and 4 hr after training did not prolong good retention performance. The temporal development of impaired retention in ANI-treated mice could not be accounted for by drug dosage, duration of protein synthesis inhibition, or nonspecific sickness at test. In contrast to the suggestion that protein synthesis inhibition prolongs short-term memory, the results of this experiment indicate that short-term memory is not prolonged by antibiotic drugs that inhibit cerebral protein synthesis. All evidence seems consistent with the hypothesis that short-term memory is independent of protein synthesis and that the establishment of long-term memory depends on protein synthesis during or shortly after training.

Three age groups of male Swiss albino CD-1 mice (2-3 mo, 6-7 mo, and 14-15 mo) were treated with a 120 mg/kg dose of the protein synthesis inhibitor anisomycin or with an equal volume of saline at various times before and after training (20 min pretraining, 0, 10, 30, or 180 min posttraining) in a shock motivated passive-avoidance task. Young (2-3 mo) and intermediate-aged (6-7 mo) mice treated with anisomycin before or immediately after training demonstrated impaired retention at a 7 day test, but retention was normal for mice injected 10, 30 or 180 min posttraining. The older mice (14-15 mo) showed similar results, with one exception: those older mice injected with anisomycin 10 min posttraining were significantly impaired in retention as compared to older saline controls and to identically treated young or intermediate-age mice. The prolonged gradient of retrograde amnesia demonstrated by older mice could not be accounted for by impaired acquisition, impaired short-term memory, altered spontaneous locomotor activity, or differential inhibition of brain protein synthesis.