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-trial inhibitory avoidance training, hindered memory of the avoidance task measured 24 h later. The effect was seen regardless of the intensity of the avoidance training footshock. The effect was not seen if the exposure to novelty 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 accordingly. The amnesic effect of the novelty presented 1 h after avoidance training was blocked by the intrahippocampal infusion of D-2-amino-5-phosphono-pentanoic acid (AP5, 25 nmoles per side) or 1-(N, O-bis-[5-isoquinolinylsulphonyl]-N-methyl-L-tyrosyl)-4- phenylpiperazine (KN62, 100 micromoles per side) but not by that of C32H25N3O6 (KT5720, 90 micromoles per side) given 5 min before the novelty. In the open field there was habituation, measured by the decrease in exploration between the first and second minute. AP5 and KN62 impaired this habituation, but not KT5720. Exploration of the open field was similar 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 tasks: novelty was amnesic for the one-trial avoidance task, but the opposite 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 habituation learning.