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. 2015 Mar 13;40(5):1278-88.
doi: 10.1038/npp.2014.315.

A Diet Enriched With Curcumin Impairs Newly Acquired and Reactivated Fear Memories

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Free PMC article

A Diet Enriched With Curcumin Impairs Newly Acquired and Reactivated Fear Memories

Melissa S Monsey et al. Neuropsychopharmacology. .
Free PMC article

Abstract

Curcumin, a yellow-pigment compound found in the popular Indian spice turmeric (Curcuma longa), has been extensively investigated for its anti-inflammatory, chemopreventative, and antidepressant properties. Here, we examined the efficacy of dietary curcumin at impairing the consolidation and reconsolidation of a Pavlovian fear memory, a widely studied animal model of traumatic memory formation in posttraumatic stress disorder (PTSD). We show that a diet enriched with 1.5% curcumin prevents the training-related elevation in the expression of the immediate early genes (IEGs) Arc/Arg3.1 and Egr-1 in the lateral amygdala (LA) and impairs the 'consolidation' of an auditory Pavlovian fear memory; short-term memory (STM) is intact, whereas long-term memory (LTM) is significantly impaired. Next, we show that dietary curcumin impairs the 'reconsolidation' of a recently formed auditory Pavlovian fear memory; fear memory retrieval (reactivation) and postreactivation (PR)-STM are intact, whereas PR-LTM is significantly impaired. Additional experiments revealed that dietary curcumin is also effective at impairing the reconsolidation of an older, well-consolidated fear memory. Furthermore, we observed that fear memories that fail to reconsolidate under the influence of dietary curcumin are impaired in an enduring manner; unlike extinguished fear memories, they are not subject to reinstatement or renewal. Collectively, our findings indicate that a diet enriched with curcumin is capable of impairing fear memory consolidation and reconsolidation processes, findings that may have important clinical implications for the treatment of disorders such as PTSD that are characterized by unusually strong and persistently reactivated fear memories.

Figures

Figure 1
Figure 1
Dietary curcumin impairs the consolidation of an auditory fear memory. (a) Schematic of the behavioral protocol. (b) Mean (±SEM) immunoreactivity for Arc/Arg3.1 and Egr-1 proteins in the LA of Chow/Naive (n=10), Curcumin/Naive (n=10), Chow/Fear Conditioned (FC; n=10), and Curcumin/FC (n=10) groups 120 min after training. Representative blots can be seen in the inset. Here, IEG protein levels have been normalized to GAPDH levels for each sample. Each protein is expressed as a percentage of the Chow/Naive group. *P<0.05, relative to the Chow/Naive group. (c) Mean (±SEM) postshock freezing in Chow (n=6) and Curcumin (n=6) groups immediately after the conditioning trials. (d) Mean (±SEM) STM assessed at 2 h after conditioning in each group. (e) Mean (±SEM) LTM assessed 24 h after conditioning in each group (Chow vs Curcumin; p<0.05).
Figure 2
Figure 2
Dietary curcumin impairs the reconsolidation of an auditory fear memory. (a) Schematic of the behavioral protocol. (b) Mean (±SEM) postshock freezing in Chow (n=6) and Curcumin (n=6) groups immediately after the conditioning trials. (c) Mean (±SEM) percent freezing in each group during the reactivation trial. *P<0.05 relative to the pre-CS period. (d) Mean (±SEM) PR-STM assessed 2 h after the reactivation trial in each group. (e) Mean (±SEM) PR-LTM assessed 24 h after the reactivation trial in each group (Chow vs Curcumin; p<0.05).
Figure 3
Figure 3
Dietary curcumin has no effect on a nonreactivated fear memory. (a) Schematic of the behavioral protocol. (b) Mean (±SEM) postshock freezing in Chow (n=8) and Curcumin (n=8) groups immediately after the conditioning trials. (c) Mean (±SEM) freezing in each group during the ‘no-reactivation' trial. (d) Mean (±SEM) ‘PR'-STM assessed 2 h after the no-reactivation trial in each group. (e) Mean (±SEM) ‘PR'-LTM assessed 24 h after the no-reactivation trial in each group.
Figure 4
Figure 4
Dietary curcumin impairs the reconsolidation of an older auditory fear memory. (a) Schematic of the behavioral protocol. (b) Mean (±SEM) postshock freezing in Chow (n=8) and Curcumin (n=8) groups immediately after the conditioning trials. (c) Mean (±SEM) freezing in each group during the reactivation trial. *P<0.05 relative to the pre-CS period. (d) Mean (±SEM) PR-STM assessed 2 h after the reactivation trial in each group. (e) Mean (±SEM) PR-LTM assessed 24 h after the reactivation trial in each group (Chow vs Curcumin; p<0.05).
Figure 5
Figure 5
Curcumin-induced reconsolidation impairments are not subject to reinstatement or renewal. (a) Schematic of the behavioral protocol. (b) Mean (±SEM) postshock freezing in Chow/Ext/No Reinst (n=10), Chow/Ext/Reinst (n=9), Chow/React (n=9), and Curcumin/React (n=10) groups immediately after the conditioning trials in context A. (c) Mean (±SEM) freezing in the reactivated groups during the reactivation trial in context B. *P<0.05 relative to the pre-CS period. (d) Mean (±SEM) freezing during extinction training in context B in the two groups fed a diet of regular chow. Note that one of these groups (Chow/Ext/Reinst) would later be exposed to an unsignaled shock US to reinstate the fear memory, whereas the other group (Chow/Ext/No Reinst) would not (f). (e) Mean (±SEM) freezing in each group in context B during the initial retention test 24 h after reactivation or extinction trials. (f) Mean (±SEM) PSF in each group during the reinstatement session in context C. (g) Mean (±SEM) freezing during the second tone test (Reinstatement Test) given in context B 24 h after the reinstatement session. Note that the fear memory has returned in the Chow/Ext/Reinst group, but not in the Curcumin/React group. (h) Mean (±SEM) freezing during the third tone test (renewal test) given in context D 24 h after the Reinstatement Test. Note that the fear memory has returned in the both of the extinction groups, but not in the Curcumin/React group.

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