Acute effects of AT1 receptor blockade on approach-avoidance of negative emotional faces

Journal article

Recent evidence implicates the renin angiotensin system (RAS) in various cognitive markers of depression, including dysfunctional reward processing. Yet, it remains unknown whether these effects extend to other markers implicated in depression and its treatment, such as approach-avoidance motivations that reflect innate drives to approach reward and evade harm. We sought to examine the impact of acute losartan, an angiotensin type 1 (AT1) receptor blocker, on the implicit approach-avoidance of facial expressions and checkerboard controls in healthy adults. In a randomized controlled trial, N = 68 healthy adults aged 18-50 (49 F/19 M) were administered a single 50 mg dose of losartan or placebo before completing an implicit Approach Avoidance Task (AAT) at drug-peak level. On the AAT, participants responded to color-filtered facial stimuli (happy, sad, angry, or neutral) and checkerboard controls using a joystick, and were instructed to pull all gray photos and push all brown photos as quickly as possible. Compared to placebo, losartan induced a significant avoidance bias for sad faces (p = 0.027) and reduced avoidance of angry faces at trend level (p = 0.085). This occurred without significant group differences on blood pressure, overall reaction time, accuracy, and approach-avoidance biases for other stimuli. The response pattern associated with AT1 receptor blockade may counteract previously observed depressive tendencies, suggesting effects possibly consistent with antidepressant treatments. Our findings further highlight the RAS as a mechanistically relevant target for psychiatry, suggesting that AT1 receptor antagonism may have relevance for treating depression and other emotional disorders characterized by aberrant motivational biases (Clincialtrials.gov ID: NCT06624904).

Authors: Prasad, D; Pelster, I; Outes, L; Gillespie, A; Pizzagalli, DA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: Neuropsychopharmacology
• Publication date: 2026-09-15
• Acceptance date: 2026-08-28
• DOI: 10.1038/s41386-026-02554-4
• EISSN: 1740-634X
• ISSN: 0893-133X
• Language: English
• Keywords: Major depressive disorder; Stimulus (psychology); Receptor; Cognition; Placebo; Losartan; Amygdala; Blockade