Delayed emergence of effects of memory-enhancing drugs: implications for the dynamics of long-term memory.
Many theories of memory postulate that processing of information outlasts the learning situation and involves several different physiological substrates. If such physiologically distinct mechanisms or stages of memory do in fact exist, they should be differentially affected by particular experimental manipulations. Accordingly, a selective improvement of the processes underlying short-term memory should be detectable only while the information is encoded in the short-term mode, and a selective influence on long-term memory should be detectable only from the moment when memory is based on the long-term trace. Our comparative study of the time course of the effects of the cholinergic agonist arecoline, the gamma-aminobutyric acid type B receptor antagonist CGP 36742, the angiotensin-converting enzyme inhibitor captopril, and the nootropic 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 memory only after 16-24 h. From the observation that animals also show clear signs of retention during the first 16 h--i.e., before the effects of the substances are measurable--it can be inferred that retention during this time is mediated by other mechanisms that are not influenced by any of the substances.
Mondadori
C
C
Pharmaceutical Research Division, CIBA-Geigy Limited, Basle, Switzerland.
Hengerer
B
B
Ducret
T
T
Borkowski
J
J
D000818:Animals; D001115:Arecoline / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D013997:Time Factors
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011619:Psychotropic Drugs; D011759:Pyrrolidines; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D001115:Arecoline; D002216:Captopril; C040619:oxiracetam