Previous studies have shown that amygdala-dependent fear memories that are lost due to interference with the reconsolidation process are lost in an enduring manner; they are not sensitive to spontaneous recovery, reinstatement, or renewal in a new testing LY2835219 citations context. Here, we asked whether the reconsolidation deficit induced by garcinol is similarly insensitive to spontaneous recovery, reinstatement, or to a shift in the testing context. Rats were fear conditioned as before followed 24 h later by a reactivation trial in a distinct context. While the study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has attracted considerable experimental interest, few compounds have to date emerged that are readily useful in a clinical setting. Recent studies, however, have suggested that the targeting of ��epigenetic�� processes, including modifications in chromatin structure and function, may hold considerable promise in the treatment of neuropsychiatric diseases that affect memory and cognition. In this study, we have systematically investigated the potential efficacy of garcinol, a naturally-occurring 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 PTSD. We show that local infusion of garcinol into the LA, the presumed locus of storage of fear memories, impairs the training and retrieval-related acetylation of histone H3 in the LA. We further show that intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory recall, respectively, significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Garcinol is a polyisoprenylated benzophenone compound extracted from the rind of the fruit of Garcinia indica, also known as Kokum, a tree native to the tropical coastal regions of Western India. While typically not eaten as a fresh fruit, Kokum rind is instead frequently dried and used as a seasoning for curries or processed into a syrup suitable for drinking. The readily consumable juice made from the rind of the Kokum fruit has been prevalently used in Ayurvedic medicine to treat a remarkably wide range of ailments, including inflammation, infection, dermatitis, and gastrointestinal problems. Empirical studies have further identified anti-oxidant, anti-obesity, SCH772984 anti-tumor and anti-inflammatory actions of garcinol or its derivatives. While there are over a dozen existing patents for the potential efficacy of garcinol in the treatment of various conditions ranging from inflammation to obesity to cancer, our findings are the first to suggest that garcinol may also be effective, either alone in combination with existing pharmacological or behavioral interventions, in the treatment of neuropsychiatric disorders such as PTSD.