Acute angiotensin II receptor blockade facilitates parahippocampal processing during memory encoding in high-trait-anxious individuals

Journal article

Background

Angiotensin II receptor blockers (ARBs) have been associated with preventing posttraumatic stress disorder symptom development and improving memory. However, the underlying neural mechanisms are poorly understood. This study investigated ARB effects on memory encoding and hippocampal functioning that have previously been implicated in posttraumatic stress disorder development.

Methods

In a double-blind randomized design, 40 high-trait-anxious participants (33 women) received the ARB losartan (50 mg) or placebo. At drug peak level, participants encoded images of animals and landscapes before undergoing functional magnetic resonance imaging, where they viewed the encoded familiar images and unseen novel images to be memorized and classified as animals/landscapes. Memory recognition was assessed 1 hour after functional magnetic resonance imaging. To analyze neural effects, whole-brain analysis, hippocampus region-of-interest analysis, and exploratory multivariate pattern similarity analysis were employed.

Results

ARBs facilitated parahippocampal processing. In the whole-brain analysis, losartan enhanced brain activity for familiar images in the parahippocampal gyrus (PHC), anterior cingulate cortex, and caudate. For novel images, losartan enhanced brain activity in the PHC only. Pattern similarity analysis showed that losartan increased neural stability in the PHC when processing novel and familiar images. However, there were no drug effects on memory recognition or hippocampal activation.

Conclusions

Given that the hippocampus receives major input from the PHC, our findings suggest that ARBs may modulate higher-order visual processing through parahippocampal involvement, potentially preserving intact memory input. Future research needs to directly investigate whether this effect may underlie the preventive effects of ARBs in the development of posttraumatic stress disorder.

Authors: Shkreli, L; Thoroddsen, T; Kobelt, M; Martens, MAG; Browning, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Biological Society Global Open Science
• Volume: 4
• Issue: 2
• Article number: 100286
• Place of publication: United States
• Publication date: 2023-12-25
• Acceptance date: 2023-12-14
• DOI: 10.1016/j.bpsgos.2023.100286
• EISSN: 2667-1743
• Pmid: 38323154
• Language: English
• Keywords: posttraumatic stress disorder; losartan; pattern-similarity analysis; angiotensin ii receptor blocker; parahippocampus; memory encoding