The b-adrenergic antagonist propranolol is an exception to this rule and has received considerable experimental attention for its ability to impair both newly formed and reactivated fear memories in preclinical studies. However, propranolol has not been shown to be effective in every study, and its effectiveness in treating symptoms of PTSD in humans has yielded mixed results. It is thus of considerable interest to investigate the efficacy of other compounds that are similarly 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. In recent years, interest has turned toward the examination of a relatively new class of pharmacological agents that target so-called ��epigenetic�� processes in the treatment of neuropsychiatric disorders. Epigenetic modifications, including alterations in chromatin structure and DNA methylation, have been widely implicated in BU 4061T memory and cognition. Chromatin, which consists of DNA packaged tightly around a core of eight histones, is known to be dynamically regulated by acetylation of histones via histone acetyltransferases. Acetylation causes chromatin structure to relax, leading to enhanced transcription, a process that is readily reversible via a second family of chromatin modifying enzymes known as histone deacetylases. In a clinical context, studies have suggested that enhancing histone acetylation through HDAC inhibition can rescue the memory Ruxolitinib purchase deficits associated with cognitive disorders ranging from certain forms of intellectual disabilities to Alzheimer��s disease. However, while enhancing histone acetylation has shown promise for treating neuropsychiatric disorders characterized by memory impairment, traumatic fear memories are an example of a memory-related psychiatric disorder in which it is desirable to impair, rather than enhance, the memory trace. In the present study, we explore the potential efficacy of a relatively novel and naturally-occurring HAT inhibitor known as garcinol, derived from the rind of the fruit of the Kokum tree, in the treatment of newly formed and reactivated fear memories. We show that garcinol impairs histone acetylation in the lateral nucleus of the amygdala associated with fear conditioning and retrieval of a fear memory. Further, we show that intra-LA or systemic administration of garcinol within a narrow time window after fear conditioning or fear memory retrieval impairs the consolidation and reconsolidation of a fear memory in a time-limited and retrieval-specific manner. Collectively, our findings suggest the intriguing possibility that a naturally-occurring compound derived from the diet may be useful in the treatment of newly acquired or recently reactivated traumatic memories. Our experiments thus far collectively suggest that local infusion of garcinol into the LA impairs reconsolidation of an auditory fear memory in a time-limited and retrieval-specific manner.