Reduction of aversive learning rates in Pavlovian conditioning by angiotensin II antagonist losartan: a randomised controlled trial

Abstract

The angiotensin receptor blocker losartan has been linked to aspects of aversive learning such as fear acquisition and extinction, inhibition of aversive learning rates and reduced post-traumatic stress disorder (PTSD) symptoms. Here, we investigate the influence of losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized placebo-controlled design, we tested 45 healthy volunteers during a baseline session (session 1), after application of losartan or placebo (session 2) and during a follow-up session (session 3). On each session, participants engaged in a task where they had to predict the likelihood of an electrical stimulation on every trial while the true shock contingencies repeatedly switched between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Acute administration of losartan significantly reduced participants’ adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates on the drug session compared to baseline. The 50mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out general reduction in attention and engagement. Decreased adjustment of aversive expectations to low-to-high, but not high-to-low, threat change was maintained on a follow up session 24hrs later, suggesting a possible role of losartan in prevention of formation of aversive associations on longer time scales.