Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development. We investigated the influence of the angiotensin receptor blocker losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized, 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. During each session, participants engaged in a task in which they had to predict the probability of an electrical stimulation on every trial while the true shock contingencies switched repeatedly 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 in the losartan group during the drug session compared with baseline. The 50-mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out a general reduction in attention and engagement. Decreased adjustment of aversive expectations was maintained at a follow-up session 24 hours later. This study shows that losartan acutely reduces Pavlovian learning in aversive environments, thereby highlighting a potential role of the renin-angiotensin system in anxiety development.

中文翻译：

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血管紧张素 II 拮抗剂氯沙坦降低巴甫洛夫条件反射中的厌恶学习率：一项随机对照试验

血管紧张素受体阻断与厌恶性学习和记忆形成以及预防创伤后应激障碍症状的发展有关。我们使用概率学习范式研究了血管紧张素受体阻滞剂氯沙坦对厌恶性巴甫洛夫条件反射的影响。在双盲、随机、安慰剂对照设计中，我们在基线疗程、应用氯沙坦或安慰剂（药物疗程）后以及后续疗程期间对 45 名（18 名女性）健康志愿者进行了测试。在每次会议期间，参与者都参与一项任务，其中他们必须预测每次试验中电刺激的概率，而真正的电击意外事件在高电击威胁和低电击威胁阶段之间反复切换。计算强化学习模型用于研究学习动态。氯沙坦的快速给药显着减少了参与者在从低到高和从高到低的威胁变化期间的调整。这是由于与基线相比，氯沙坦组在药物治疗期间的厌恶学习率降低所致。 50 毫克的药物剂量不会导致血压降低或反应时间改变，排除了注意力和参与度普遍下降的可能性。 24 小时后的后续会议中，仍维持厌恶预期的减少调整。这项研究表明，氯沙坦会急剧降低厌恶环境中的巴甫洛夫学习，从而强调肾素-血管紧张素系统在焦虑发展中的潜在作用。