Forget the stress: retrograde amnesia for the stress-induced impairment of extinction retrieval

Abstract

We investigated whether cycloheximide (CHX) would induce amnesia for the stress-induced impairment of extinction retrieval. First, a single restraint stress session was demonstrated to impair extinction retrieval, but not fear conditioning. A second experiment showed that when CHX was administered immediately after restraint, rats exhibited significant extinction retrieval at test (i.e., retrograde amnesia for the stress). In a third experiment, the stress session impaired various amounts of extinction durations, suggesting that the stress inhibited extinction retrieval rather than enhancing the original fear learning. These results suggest memories for acute stress are susceptible to disruption, which could have clinical implications.

Figure 1.

Mean (±SEM) latency to cross to the black side of the black–white shuttle box in seconds for all groups in Experiment 1. Long latency scores for the No Ext, Stress/No Ext, and Stress/Ext groups represent significant fear. Decreased latency scores for the group that did not receive stress before training and extinction (Extinction) represents a significant reduction of fear. Increased latency scores for the group that received stress 48 h before training (Stress/Ext) compared to the no stress extinction group (Extinction) represents the stress induced impairment of extinction.

Figure 2.

Mean (±SEM) latency to cross to the black side of the black–white shuttle box in seconds for both groups in Experiment 2. Longer latency scores for the Saline group that was stressed 48 h prior to training replicates the stressed induced impairment of extinction. Decreased latency scores for the group injected with CHX following stress compared to the increased scores for the Saline group shows retrograde amnesia for the stress memory.

Figure 3.

Mean (±SEM) latency to cross to the black side of the black–white shuttle box in seconds for all groups in Experiment 3. Dark bars represent the no stress control groups. Light shaded bars represent the stressed experimental groups. Long latency scores for the two No Ext control groups represent significant fear. Shorter latency scores for the No Stress extinction groups represents significant extinction. The longer latencies for the Stress extinction groups demonstrate that stress prior to training and extinction impaired the various amounts of cue exposure duration.