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. 2007 Jul 1;62(1):33-9.
doi: 10.1016/j.biopsych.2006.09.009. Epub 2007 Jan 3.

Persistent Disruption of a Traumatic Memory by Postretrieval Inactivation of Glucocorticoid Receptors in the Amygdala

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Free PMC article

Persistent Disruption of a Traumatic Memory by Postretrieval Inactivation of Glucocorticoid Receptors in the Amygdala

Sophie Tronel et al. Biol Psychiatry. .
Free PMC article

Abstract

Background: Posttraumatic stress disorder (PTSD) is characterized by acute and chronic changes in the stress response, which include alterations in glucocorticoid secretion and critically involve the limbic system, in particular the amygdala. Important symptoms of PTSD manifest as a classical conditioning to fear, which recurs each time trauma-related cues remind the subject of the original insult. Traumatic memories based on fear conditioning can be disrupted if interfering events or pharmacological interventions are applied following their retrieval.

Methods and results: Using an animal model, here we show that a traumatic memory is persistently disrupted if immediately after its retrieval glucocorticoid receptors are inactivated in the amygdala. The disruption of the memory is long lasting and memory retention does not re-emerge following strong reminders of the conditioned fear.

Conclusions: We propose that a combinatorial approach of psychological and pharmacological intervention targeting the glucocorticoid system following memory retrieval may represent a novel direction for the treatment of PTSD.

Figures

Figure 1
Figure 1. Photomicrograph of a representative cannula placement and schematic representations of injection sites into the BLA at the indicated rostrocaudal planes
The numbers represent the coordinates from bregma (in millimeters) according to Paxinos and Watson (1998). Injections sites were contained within the black circle. BLA: basolateral amygdaloid nucleus, anterior part; BLP: basolateral amygdaloid nucleus, posterior part.
Figure 2
Figure 2. Injection of 0.3 ng of RU 38486 in the BLA after recall has no effect on IA memory retention
Latency to enter the shock chamber was taken as a measure of memory retention. Rats were trained in IA (Tr) and tested 2 days later (Test 1). This test recalled the memory. Immediately after Test 1, 0.3 ng of RU 38486 or the same volume of vehicle solution was bilaterally injected (↑) into the BLA. IA memory was tested again 2 days later (Test 2). No difference was observed between groups at Test 2.
Figure 3
Figure 3. Injection of 1.2 ng of RU 38486 in the BLA after recall disrupts IA memory
Latency to enter the shock chamber was taken as a measure of memory retention. Rats were trained in IA (Tr) and memory was recalled by testing 2 days later (Test 1). Immediately after Test 1, 1.2 ng of RU 38486 or the same volume of vehicle was bilaterally injected (↑) into the BLA. IA memory was tested again 2 days later (Test 2). RU 38486 injections impaired memory retention at Test 2 compared to vehicle or Test 1 latencies (**, P < 0.01). Injection of RU 38486 in the absence of memory reactivation had no effect.
Figure 4
Figure 4. GR-antagonist-dependent disruption of a reactivated IA memory is long-lasting and memory does not recover following a shock reminder
Latency to enter the shock chamber was taken as a measure of memory retention. Rats were trained in IA (Tr) and memory was recalled by testing 2 days later (Test 1). Immediately after Test 1, 1.2 ng of RU 38486 or the same volume of vehicle was bilaterally injected (↑) into their BLA. IA memory was tested 2 days (Test 2) and 1 weeks later (Test 3). Immediately after Test 3, the rats were exposed to a reminder shock. Memory was tested again 1 day later (Test 4). RU 38486-injected group showed a significantly lower retention at Test 2, Test 3 and Test 4 compared to the vehicle-injected group (**; P < 0.01).
Figure 5
Figure 5. The amnesic animals that received bilateral injection of RU 38486 in the BLA after recall can re-learn amygdala-dependent tasks
Latency to enter in the shock chamber was taken as a measure of memory retention. Rats were trained in IA (Tr) and memory was recalled by testing 2 days later (Test 1). Immediately after Test 1, 1.2ng of RU 38486 or the same volume of vehicle solution was bilaterally injected (↑) into the BLA. IA memory was tested again 2 days later (Test 2). The RU 38486-injected group was retrained three hours later with IA and tested 2 days later (Test 3). The group that received RU 38486 injections showed memory impairment at Test 2 compared to vehicle-injected or Test 1 (***, P<0.001). When exposed to another IA training session, the amnesic rats re-learned IA. At Test 3, the RU 38486-injected rats showed significant memory retention compared to the impairment found at Test 2 (***, P < 0.001).

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