Amnesia was induced by pretraining injections of cycloheximide (CYC) in a food motivated discrimination reversal task. Magnitude of amnesia varied as a function of the amount of training on both the initial discrimination and the reversal and also as a function of the length of intertrial interval used on both the reversal and the test. Memory spontaneously recovered 48 hr. following reversal training. Recovery from amnesia was induced by pretesting injections of d-amphetamine and 2 monoamine oxidase inhibitors, pargyline and catron. This enhanced performance was a true recovery of the memory and not a result of enhanced learning or increased arousal. Depletion of catecholamines by alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, and diethyldithiocarbamate, a dopamine beta hydroxylase inhibitor, resulted in an amnesia quantitatively and qualitatively similar to amnesia induced by CYC. These data support the hypothesis that CYCinduced amnesia is mediated via central catecholamines.

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The amnesic effects of cycloheximide (CYC) on habits of different ages were investigated in a food-motivated, discrimination-reversal task. Groups of C57BL/6J mice were injected 30 min before training or immediately, 3 days, 6 days, or 9 days after training. Retention was tested 24 hr after CYC treatment. The usual amnesic effect of CYC occurred in animals injected before training. No amnesia was apparent in groups injected immediately, 3 days, or 9 days after training. However, a reliable and reproducible amnesia occurred in the group injected 6 days after training. This amnesia could be reversed by pretest treatment with a monoamine oxidase inhibitor, pheniprazine. Pheniprazine, given 7 days after training, also enhanced retrieval of memory in saline-injected mice.Although amnesia can sometimes result from posttraining injections of cycloheximide (CYC) or acetoxycycloheximide (AXM) (e.g., Geller, Robustelli, Barondes, Cohen, & Jarvik, 1969;Quartermain & McEwen, 1970), the majority of experiments employing multiple-trial tasks failed to demonstrate amnesia when CYC or AXM is given after training (e.g., Barondes & Cohen, 1967;Daniels, 1972;Flexner & Flexner, 1966;Squire & Barondes, 1972). These findings have led to a general acceptance of the notion that protein synthesis must be inhibited while learning is taking place in order for an impairment in memory to be subsequently demonstrated.The ineffectiveness of posttraining CYC treatment in multiple-trial tasks is most commonly accounted for by reference to the consolidation hypothesis. Briefly, this hypothesis assumes that by the time the training trials are terminated, or shortly thereafter, the memory trace has consolidated into a storage stage (either intermediate or long-term memory), which is no longer susceptible to disruption by protein-synthesis inhibition (McGaugh, 1966(McGaugh, , 1968). An alter-This study was supported by Grant Foundation, Incorporated. We thank G. B. Whitfleld of the Upjohn Company forsupplying the cycloheximide.Requests for reprints should be sent to David