Nitric Oxide Is Necessary for Multiple Memory Processes after Learning That a Food Is Inedible in Aplysia

Nitric oxide (NO) signaling was inhibited viaNω-nitro-l-arginine methyl ester(l-NAME) during and after training Aplysiathat a food is inedible. Treating animals with l-NAME 10 min before the start of training blocked the formation of three separable memory processes: (1) short-term, (2) intermediate-term, and (3) long-term memory. The treatment also attenuated, but did not block, a fourth memory process, very short-term memory. l-NAME had little or no effect on feeding behavior per se or on most aspects of the animals' behavior while they were being trained, indicating that the substance did not cause a pervasive modulation or poisoning of many aspects of feeding and other behaviors. Application ofl-NAME within 1 min after the training had no effect on short- or long-term memory, indicating that NO signaling was not needed during memory consolidation. Treating animals with the NO scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazdine-1-oxy-3-oxide before training also blocked long-term memory. Memory was not blocked byd-NAME, or by the simultaneous treatment withl-NAME and the NO donorS-nitroso-N-acetyl-penicillamine, confirming that the effect of l-NAME is attributable to its effect as a competitive inhibitor of l-arginine for NO synthase in the production of NO rather than to possible effects at other sites. These data indicate that NO signaling during training plays a critical role in the formation of multiple memory processes.