Modulation of the renin-angiotensin system inhibits memory advantage for negative emotional material via decreasing hippocampus activation and its coupling with the amygdala

Abstract

AbstractExaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of post-traumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy and preventing the dysregulations already during exposure to threatening events may attenuate the development of PTSD-symptomatology. The present proof-of-concept study examined the potential of a single dose of the angiotensin II type 1 receptor (AT1R) antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism. In a preregistered double-blind, between-subject, placebo-controlled pharmaco-fMRI study we combined an emotional subsequent memory paradigm with LT (n=29) or placebo treatment (n=30) and a surprise memory test after 24h washout. LT generally improved memory performance and abolished emotional memory enhancement for negative yet not positive material while emotional experience during encoding remained intact. LT further suppressed the hippocampus activity during encoding of subsequently remembered negative stimuli and abolished the positive association between higher activity in this region and subsequent better memory for negative material observed under placebo. On the network level LT reduced coupling between the hippocampus and the basolateral amygdala during successful encoding of negative stimuli. Overall, our findings suggest that LT has the potential to selectively attenuate memory formation for negative yet not positive information by decreasing hippocampus activity and its functional coupling strength with the left 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.