Retrograde Amnesia Induced by Drugs Acting on Different Molecular Systems

The gamma aminobutyric acid-A (GABA A ) agonist, muscimol, the glutamate N- methyl- D -aspartate (NMDA) receptor antagonist, D -2-amino-5-phosphonopentanoic acid (AP5), and the inhibitor of the extracellularly regulated kinases (ERKs), U0 126, cause retrograde amnesia when administered to the hippocampus. In the present study, the authors found that they all cause retrograde amnesia for 1-trial inhibitory avoidance, not only when infused into the dorsal CA1 region of the hippocampus, but also when infused into the basolateral amygdala or the entorhinal, parietal, and posterior cingulate cortices. The posttraining time course of the effect of each drug was, however, quite different across brain structures. Thus, in all of them, NMDA receptors and the ERK pathway are indispensable for memory consolidation, and GABA A receptor activation inhibits memory consolidation; but in each case, their influence is interwoven differently.