부산대학교 도서관

Facilitation of fear extinction and inhibition of reconsolidation of fear memory are useful for the treatment of fear-related disorders, such as post-traumatic stress disorder (PTSD). Here, we investigated the effects of two DOP agonists, KNT-127 and SNC80, with different chemical structures on the fear extinction and reconsolidation of fear memory in mice. On day 1, male C57BL/6J mice were contextually conditioned with 8 footshocks. On day 2, the mice were re-exposed to the conditioning chamber as a memory retrieval session (re-exposure 1). DOP agonists were administered subcutaneously 30 min before (for extinction) or immediately after (for reconsolidation) the re-exposure 1. On day 3, mice were re-exposed to the chamber as a memory testing session (re-exposure 2). The duration of re-exposure was 6 min for extinction and was 2 min for reconsolidation. As a result, KNT-127 (3–10 mg/kg), but not SNC80 (1–10 mg/kg), administered to the mice following both 6-min and 2-min re-exposure 1 significantly decreased the freezing rates of mice during re-exposure 2. These effects of KNT-127 were abolished by pretreatment with a selective DOP antagonist. In conclusion, we propose that KNT-127 facilitates fear extinction and inhibits reconsolidation of fear memory via DOP.