Time-dependent effects of cycloheximide on long-term memory in the cuttlefish.

When shown prawns in a glass tube, cuttlefish promptly learn to inhibit their predatory behavior and retain this ability for a long time. The cellular and molecular mechanisms of this long-term memory (LTM) are not yet known. In this study, we analyzed the dependency of LTM on de novo brain protein synthesis. Cycloheximide (CXM), a protein synthesis inhibitor, is injected intravenously immediately, 1 h, 3 h, 4 h or 6 h after the training. Retention is tested 24 h posttraining. The injections of CXM revealed one period of memory sensitivity to pharmacological intervention. CXM administered immediately or 6 h after training has no effect on LTM. Conversely, injections given between 1 and 4 h posttraining resulted in amnesia. Taken together, findings of this study establish for the first time in Sepia officinalis that de novo protein synthesis is an essential and time-dependent event for LTM formation of this form of associative learning.