Losartan Modulates Neural Responses to Looming Visual Stimuli: An Eye-tracking Study

Losartan Modulates Neural Responses to Looming Visual Stimuli: An Eye-tracking Study

The main aim of the present study is to investigate the effects of orally administered losartan on the perception of time-to-collision of threatening and non-threatening stimuli by combining a validated looming fear eye-tracking paradigm with a randomized between-subject placebo-controlled pharmacological trial design.

Animal models and initial findings in humans suggest a role of the angiotensin II antagonist losartan in socio- emotional processes. At the same time, the visual system's remarkable ability to perceive and interpret impending threats, notably through the "looming" phenomenon- a distinct pattern of optical expansion on the retina as objects approach, theoretically allows for precise estimation of the time-to-collision (TTC). It was demonstrated that the affective content of looming stimuli influences perceived TTC, with threatening objects judged as approaching sooner than non-threatening objects, hinting at a nuanced interaction between emotional valence and temporal perception. Within this context the present study aims to examine whether angiotensin II blockade via Losartan modulates the perception of time-to-collision towards threatening and non-threatening stimuli. To this end, healthy individuals will undergo a double-blind, between-subjects, placebo-controlled pharmaco-eye-tracking experiment and receive a single oral dose of losartan (50 mg) or placebo before performing a looming fear task 90 minutes after administration. The task paradigm will encompass threatening (butterfly, rabbit) and non-social (spider, snake) stimuli to examine the emotion-specific effects of losartan.

Inclusion Criteria:

• Healthy subjects who volunteer to participate and are able to fully understand and agree with this study by written informed consent.
• Normal or corrected-normal version

Exclusion Criteria:

• History of neuropsychiatric diseases.
• History of cardiac disease, including arrhythmias, aortic stenosis, or congestive heart failure; history of syncope or unexplained loss of consciousness.
• History of hepatic diseases, including cholestasis, biliary obstructive disease, or severe liver dysfunction.
• History of renal diseases, including renal stones or renal failure.
• History of hyponatremia(Serum sodium <135mmol/L) or hyperkalemia (Serum potassium>5.5mmol/L); history of diabetes mellitus or diabetes insipidus
• Known hypersensitivity or allergic reaction to any medication or hormone; strong allergic reaction to food.
• Infections such as COVID-19 or influenza, or unexplained fever.
• Subjects with hypertension (BP ≥130/80mmHg) or hypotension (BP ≤ 90/60mmHg).
• History of alcohol or drug abuse; smoker (≥ 10 cigarettes or ≥ 3 cigars or ≥ 3 pipes/day); smoker using e-cigarettes.
• Blood donation (≤ 1 month prior to administration).
• Take oral contraceptives or receive hormonal medications in the three months prior to the experiment.