Suppression of Fear Memory Reinstatement by 3,6′-Disinapoyl Sucrose

Fear memories are easily formed but very difficult to erase, and even after extinction, they easily relapse. Post-traumatic stress disorder(PTSD) is a disorder characterized by persistent and excessive symptoms triggered by traumatic fear memories. Treatment to erase these memories is time-consuming and prone to relapse. Radix polygalae has been shown to inhibit the reinstatement and renewal of fear memories in mice. This study aimed to identify components of Radix polygalae and its optimal dose that suppresses fear reinstatement using the fear conditioning paradigm in animal models and measure the cognitive and anxiety related behaviors and molecular changes in the hippocampus. Among senegenin, TMCA, and DISS, only DISS inhibited reinstatement, and the optimal dose was 1 mg/kg. In normal mice, this dose had no effect on spatial memory or working memory, but an anxiolytic effects. Furthermore, it increased the expression of p-CREB and glucocorticoid receptors in the hippocampus. These results suggest that DISS selectively inhibits the reinstatement of fear memory without affecting other cognitive functions, and that this effect is related to its action on neurotrophic and stress-response pathways in the hippocampus. DISS will possibly be used to suppress fear memory recurrence in PTSD patients at appropriate doses.