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-microl intrahippocampal infusion of the protein-synthesis inhibitor anisomycin (80 microg) 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.

Figure 1

Schematic drawing of plane A—4.3 of the atlas of Paxinos and Watson (1986)—showing (stippled) the extent of the area reached by the infusion in the dorsal hippocampus.

Figure 2

Effects of anisomycin on retention of one-trial step-down inhibitory avoidance task in rats (foot shock intensity, 0.4 ma; training-test interval, 24 hr). Data are expressed as median (interquartile range) training and test session latencies (in sec). Animals received bilateral 0.8-μl infusions of vehicle (□) or anisomycin (▪; 80 μg) in the CA1 region of the dorsal hippocampus at different times before or post-training. n = 10–13 animals per group. (*) Significant difference when compared with control group (Mann–Whitney U test, P < 0.01). All groups, except anisomycin −15 min, showed significant training-test differences (Wilcoxon test, P < 0.01).

Figure 3

(A,B) Effects of anisomycin on enhancement of memory of step-down inhibitory avoidance task in rats pretrained in the same task (foot shock intensity, 0.2-ma; interval between sessions, 24 hr). Data of step-down inhibitory avoidance is expressed as median (interquartile range) session latencies (in seconds). Animals received bilateral 0.8-μl infusions of vehicle (□) or anisomycin (▪; 80 μg) in the dorsal hippocampus 15 min before (A) or 3 hr after (B) the second training session. n = 10–13 animals per group. There are no significant differences between groups in any of the three sessions (Mann–Whitney U test, P < 0.10). All groups showed significant difference between second training and test sessions (Wilcoxon test, P < 0.01).

Figure 4

(A,B) Effects of anisomycin on retention of one trial step-down inhibitory avoidance task in rats preexposed to the task apparatus (foot shock intensity, 0.4 ma; training-test interval, 24 hr). Retention of step-down inhibitory avoidance is expressed as median (interquartile range) session latencies (in seconds). Animals received bilateral 0.8μl infusions of vehicle (□) or anisomycin (▪; 80 μg) in the dorsal hippocampus 15 min before (A) or 3 hr after (B) training session. n = 10–13 animals per group. (*) Significant difference when compared with control group (Mann–Whitney U test, P < 0.01). All groups, except anisomycin −15 min, showed significant training-test differences (Wilcoxon test, P < 0.01).