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Angiotensin Antagonist Inhibits Preferential Negative Memory Encoding via Decreasing Hippocampus Activation and Its Coupling With the Amygdala

  • Ting Xu
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Xinqi Zhou
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Guojuan Jiao
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Yixu Zeng
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Weihua Zhao
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Jialin Li
    Affiliations
    Max Planck School of Cognition, Leipzig, Germany
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  • Fangwen Yu
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Feng Zhou
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Shuxia Yao
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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  • Benjamin Becker
    Correspondence
    Address correspondence to Benjamin Becker, Ph.D.
    Affiliations
    Clinical Hospital of the Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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      Abstract

      Background

      Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of posttraumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy, and preventing the dysregulations during exposure to threatening events may attenuate the development of PTSD symptomatology.

      Methods

      In a preregistered double-blind, between-subject, placebo-controlled pharmaco-functional magnetic resonance imaging design, this proof-of-concept study examined the potential of a single dose of the angiotensin II type 1 receptor antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism via combining an emotional subsequent memory paradigm with LT (n = 29) or placebo (n = 30) and a surprise memory test after a 24-hour washout.

      Results

      LT generally improved memory performance and abolished emotional memory enhancement for negative but not positive material, while emotional experience during encoding remained intact. LT further suppressed hippocampus activity during encoding of subsequently remembered negative stimuli. At the network level, LT reduced coupling between the hippocampus and the basolateral amygdala during successful memory formation of negative stimuli.

      Conclusions

      Our findings suggest that LT may have the potential to attenuate memory formation for negative but not positive information by decreasing hippocampus activity and its functional coupling strength with the amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD symptomatology.

      Keywords

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