Two Time Windows of Anisomycin-Induced Amnesia for Inhibitory Avoidance Training in Rats: Protection from Amnesia by Pretraining but not Pre-exposure to the Task Apparatus

Abstract

We have studied the effect of training conditions on hippocampal protein synthesis-dependent processes in consolidation of the inhibitory avoidance task. Adult male Wistar rats were trained and tested in a step-down inhibitory avoidance task (0.4 mA foot shock, 24 hr training-test interval). Fifteen minutes before or 0, 3, or 6 hr after training, animals received a 0.8-µl intrahippocampal infusion of the protein-synthesis inhibitor anisomycin (80 µg) or vehicle (PBS, pH 7.4). The infusion of anisomycin impaired retention test performance in animals injected 15 min before and 3 hr after the training session, but not at 0 or 6 h post-training. Pretraining with a low foot shock intensity (0.2 mA) 24 hr before training, prevented the amnestic effect of anisomycin injected at 15 min before or 3 hr after training. However, simple pre-exposure to the inhibitory avoidance apparatus did not alter the amestic effects of anisomycin. The results suggest that hippocampal protein synthesis is critical in two periods, around the time of, and 3 hr after training. A prior weak training session, however, which does not itself alter step-down latencies, is sufficient to prevent the amnestic effect of anisomycin, suggesting that even if not behaviorally detectable, weak training must be sufficient to produce some lasting cellular expression of the experience.

Intrahippocampal infusions of anisomycin produce amnesia: Contribution of increased release of norepinephrine, dopamine, and acetylcholine

“…These findings are consistent with those of many prior studies involving injections of protein synthesis inhibitors into the hippocampus (e.g., Bourtchouladze et al 1998;Quevedo et al 1999Quevedo et al , 2004Taubenfeld et al 2001;Barriantos et al 2002;Agnihotri et al 2004;Artinian et al 2007), as well as into other brain areas such as the amygdala (Nader et al 2000;Schafe and LeDoux 2000;Debiec et al 2002;Duvarci et al 2005;Parsons et al 2006;Milekic et al 2007), and prefrontal cortex (Santini et al 2004;Akirav and Maroun 2006;Touzani et al 2007). These reports are part of a large set of papers showing that direct brain injections of protein synthesis inhibitors produce amnesia for many tasks (cf.…”

“…In addition to amnesias produced by anisomycin injections into the amygdala, as above, anisomycin also impairs memory when administered to other memory systems, including the hippocampus, where anisomycin impairs inhibitory avoidance memory (Quevedo et al 1999;Debiec et al 2002;Milekic et al 2006). The present study extends the prior findings ) in several respects.…”

Social recognition memory requires two stages of protein synthesis in mice

“…Aversive stimulation has been shown to induce a second stage of protein synthesis that reaches a significantly increased level 4-8 h after stimulus presentation (Grecksch and Matthies 1980;Freeman et al 1995;Quevedo et al 1999;Ressler et al 2002). Therefore, we administered ANI at 3, 6, and 18 h after sampling.…”

“…Evidence has accumulated showing that long-term memory storage requires protein synthesis (Freeman et al 1995;Rose 1995;Quevedo et al 1999;Rose and Stewart 1999). However, in the search for the molecular constituents of such a "memory trace" in the brain, the behavioral tasks used have focused on associative learning (e.g., fear conditioning and avoidance learning).…”

“…However, in the search for the molecular constituents of such a "memory trace" in the brain, the behavioral tasks used have focused on associative learning (e.g., fear conditioning and avoidance learning). Under certain conditions it has also been reported that two or more stages of protein synthesis are involved in memory consolidation (Grecksch and Matthies 1980;Freeman et al 1995;Quevedo et al 1999;Ressler et al 2002). However, classical (fear) conditioning and avoidance learning require negative reinforcement.…”