The neurobiological mechanisms of coping strategies avoinding generalization of fear associations in PTSD

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Ohu University
• Principal Investigator: Seki Kenjiro 奥羽大学, 薬学部, 教授 (50342803)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 過誤の恐怖記憶形成 / トラウマ記憶の汎化 / PTSD / コルチコイド受容体

Outline of Final Research Achievements

We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy-Crf-KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h). The freezing response in B-3h was intensified in the experimental mice, compared to control mice not exposed to CS, indicating that a false fear memory was formed at 3 h. The within-group freezing level at B-24h was higher than that at B-3h, indicating that false context fear memory was enhanced at B-24h. In Hy-CRF-OE mice, freezing level at B-3h was higher than that of control and Hy-Crf-KD mice, while the freezing level in B-24h was similar to that in B-3h. We hypothesized that Hy-Crf-KD potentiates the induction of false context fear memory, while Hy-CRF-OE enhances the onset of false fear memory formation.

Free Research Field

行動薬理学

Academic Significance and Societal Importance of the Research Achievements

心的外傷後ストレス障害（PTSD）では、関連性の低い状況でもトラウマ記憶が想起され（汎化）、恐怖・回避の連続による精神的苦痛を受ける。実際に恐怖体験した状況や場所と来なる環境で恐怖の再体験を繰り返すのが特徴である。一方、過誤の恐怖記憶の形成は、恐怖体験した場所と異なる環境で恐怖反応を示すという特徴がある。しかし、トラウマ記憶の汎化は恐怖体験から長期間を要するのに対し、過誤の恐怖記憶は３時間で形成されるという決定的な違いがあり、両者の関係はいまだ不明である。今後は過誤の恐怖記憶形成機序とトラウマ記憶の汎化の脳内機序を比較することで恐怖体験後のPTSD発症予防に繋がることが期待される。