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

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.