Acute angiotensin receptor blockade and mnemonic discrimination in healthy participants.

Background: The renin angiotensin system (RAS) is implicated in various cognitive processes relevant to anxiety. However, the role of the RAS in pattern separation, a hippocampal memory mechanism that enables discrete encoding of similar stimuli, is unclear. Given the proposed role of this mechanism in overgeneralization and the maintenance of anxiety, we explored the influence of the RAS on mnemonic discrimination i.e., the behavioral ability arising from pattern separation.

Design: In a double-blind experimental medicine trial, we examined the effect of losartan, an angiotensin receptor blocker, on mnemonic discrimination in N = 60 healthy volunteers aged 18-50. Participants were randomly allocated to a 50 mg losartan or placebo condition, and then completed the Mnemonic Similarity Task (MST), an established measure of pattern separation. Main outcome measures were the lure discrimination index (LDI), calculated as the rate of 'similar' responses to lures minus 'similar' responses to foils, and recognition (REC) memory, calculated as the difference between the rate of 'old' responses to targets minus 'old' responses to foils.

Results: Data were available for N = 56 participants (N = 40 females, N = 16 males). Participants in the losartan group (N = 29) achieved significantly higher LDI scores (t(54) = 2.30, p = 0.025) compared to the placebo group (N = 27), indicating better mnemonic discrimination. No significant group differences were found in REC scores (U = 324, z = -1.10, d = 0.08; p = 0.271).

Conclusions: We demonstrate for the first time that losartan improves mnemonic discrimination in healthy individuals, suggesting that the RAS may influence pattern separation and anxiety.