Abstract
The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA) impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.
Highlights
Acquired memories are thought to be inherently unstable, acquiring stability over time as they are ‘consolidated’ into long-term representations in the brain [1]
While the study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has attracted considerable experimental interest [5,6,7,8,9,10], few compounds have to date emerged that are readily useful in a clinical setting
We have systematically investigated the potential efficacy of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the diet, in mitigating the consolidation and reconsolidation of Pavlovian fear memories, a type of persistent aversive memory that is characteristic of anxiety disorders such as posttraumatic stress disorder (PTSD) [4]
Summary
Acquired memories are thought to be inherently unstable, acquiring stability over time as they are ‘consolidated’ into long-term representations in the brain [1]. Later memory retrieval is known to trigger a new phase of instability for a brief window of time during which the memory may be updated (e.g. strengthened or weakened) prior to being re-stabilized in a process known as ‘reconsolidation’ [2,3]. This window of lability for both consolidation and reconsolidation has attracted considerable experimental attention, fueled in part by the promise of discovering novel therapeutic and/or pharmacological approaches for the treatment of psychiatric disorders ranging from posttraumatic stress disorder (PTSD) to drug addiction that are characterized by unusually strong and persistent memories [4,5]. It is of considerable interest to investigate the efficacy of other compounds that are suitable for human consumption which may be used either alone or in combination with existing methods during the lability window to attenuate fearful or traumatic memories
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
