DELAYED EMERGENCE OF EFFECTS OF MEMORY-ENHANCING DRUGS - IMPLICATIONSFOR THE DYNAMICS OF LONG-TERM-MEMORY

Many theories of memory postulate that processing of information outla sts the learning situation and involves several different physiologica l substrates. If such physiologically distinct mechanisms or stages of memory do in fact exist, they should be differentially affected by pa rticular experimental manipulations. Accordingly, a selective improvem ent of the processes underlying short-term memory should be detectable only while the information is encoded in the short-term mode, and a s elective influence on long-term memory should be detectable only from the moment when memory is based on the long-term trace. Our comparativ e study of the time course of the effects of the cholinergic agonist a recoline, the gamma-aminobutyric acid type B receptor antagonist CGP 3 6742, the angiotensin converting enzyme inhibitor captopril, and the n ootropic oxiracetam, four substances with completely different primary sites of action, show that the memory-enhancing effects consistently come into evidence no sooner than 16-24 h after the learning trial. On the one hand, this finding suggests that all these substances act by way of the same type of mechanism; on the other hand, it demonstrates that the substrate modulated by the compounds forms the basis of memor y only after 16-24 h. From the observation that animals also show clea r signs of retention during the first 16 h-i.e., before the effects of the substances are measurable-it can be inferred that retention durin g this time is mediated by other mechanisms that are not influenced by any of the substances.