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

BACKGROUND: Angiotensin receptor blockade (ARB) has been linked to aspects of aversive learning and memory formation, and to the prevention of post-traumatic stress disorder symptom development. METHODS: We investigate the influence of the ARB losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomised placebo-controlled design, we tested 45 (18 female) healthy volunteers during a Baseline session, after application of losartan or placebo (Drug session) and during a Follow-up session. On each session, participants engaged in a task where they had to predict the probability 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. RESULTS: 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 in the losartan group 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 was maintained on a follow up session 24hrs later. CONCLUSIONS: This study shows that losartan acutely reduces Pavlovian learning in aversive environments, highlighting a potential role of the renin-angiotensin system in anxiety development.