Novelty causes time-dependent retrograde amnesia for one-trial avoidance in rats through NMDA receptor- and CaMKII-dependent mechanisms in the hippocampus

Exposure to a novel environment (an open field) for 2 min, 1 h after one-tr ial inhibitory avoidance training, hindered memory of the avoidance task me asured 24 h later. The effect was seen regardless of the intensity of the a voidance training footshock. The effect was not seen if the exposure to nov elty was carried out 5 min before, or 6 h after, the avoidance training, or if the animals did not perceive the open field as new and react accordingl y. The amnesic effect of the novelty presented 1 h after avoidance training was blocked by the intrahippocampal infusion of D-2-amino-5-phosphono-pent anoic acid (AP5, 25 nmoles per side) or 1-(N,O-bis-[5-isoquinolinylsulphony l]-N-methyl-L-tyrosyl)-4-phenylpiperazine (KN62, 100 mmoles per side) but n ot by that of C32H25N3O6 (KT5720, 90 mu moles per side) given 5 min before the novelty. In the open field there was habituation, measured by the decre ase in exploration between the first and second minute. AP5 and KN62 impair ed this habituation, but not KT5720. Exploration of the open field was simi lar in the groups exposed to the avoidance task 5 min later, or 1 h or 6 h before. Therefore, there was no reciprocity between the effect of the two t asks: novelty was amnesic for the one-trial avoidance task, but the opposit e was not true. The amnesic effect of novelty appears to rely on N-methyl-D -aspartate (NMDA) receptor- and calcium/calmodulin-dependent protein kinase II (CaMKII)-dependent, but not on PKA-dependent, aspects of its habituatio n learning.