Cycloheximide inhibits context memory and long-term habituation in the crab Chasmagnathus.

A shadow moving over head elicits an escape response in the crab Chasmagnathus that habituates promptly and for a long period. The effect of the protein synthesis inhibitor cycloheximide (CY) on this long-term memory was analyzed. Two hours after injection, 10 micrograms CY inhibited [14C]-amino amino acid incorporation into cerebral plus thoracic ganglia by 88% and 20 micrograms by 92%, but no inhibition was found at 24 h. A single injection of 10-20 micrograms CY given 30 min before training, failed to affect the short-term habituation. Similar doses impaired both context memory (CM) and long-term habituation (LTH) when tested at 72 and 120 h but only CM at 24 h. Such a disparity was explained by an unspecific depressing effect upon the response, attributed to an interaction between CY and training. The hypothesis was confirmed, because CY injected immediately after training disclosed amnestic effect at 24 h on both CM and LTH. A similar effect was proven when animals were injected at 2 h but not at 6 h after training. Results from experiments with pretraining and pretesting injections put aside a state-dependence or retrieval deficit effects of the drug. Taken together, findings of this article argue strongly for de novo protein synthesis as a mechanism of LTH and for the close relation between CM and LTH.