This study aims to investigate whether a single dose of losartan (50 mg) can affect learning from positive and negative outcomes and its related neural mechanisms.
Emerging evidence suggests that the renin-angiotensin system can impact dopamine (DA) transmission and its modulatory role in reward processing. For instance, recent animal models have found that the angiotensin antagonist losartan reduces rewarding effects of methamphetamine and nicotine by modulating DA release in the striatum.The present study thus will investigate losartan effects on reward reinforcement learning and the underlying neural mechanisms. In a double-blind, between-subject, placebo-controlled design, 60 healthy male subjects will be randomly assigned to receive single-dose losartan (50 mg) or placebo, 90 minutes before performing a probabilistic reinforcement learning task during fMRI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
60
administration of losartan (50 mg) (oral)
administration of placebo (oral)
University of Electronic Science and Technology of China
Chengdu, Sichuan, China
RECRUITINGBOLD-level activity as assessed by fMRI during the learning phase
During the paradigm subjects will learn the reward properties of stimuli via the presentation of trial-wise feedback. The neural activation during the prediction of positive and negative outcome feedback will be assessed by functional magnetic resonance imaging (fMRI), particularly in prefrontal and subcortical regions. The effects of treatment will be determined by comparing the losartan- and placebo-treated groups.
Time frame: 90 minutes to 110 minutes after treatment
BOLD-level activity as assessed by fMRI during the learning transfer phase
Following the initial learning phase subjects learning transfer will be examined by asking subjects to choose between stimuli with high versus low reward probabilities. The neural activation during correct responses will be assessed by functional magnetic resonance imaging (fMRI), particularly in prefrontal and subcortical regions. The effects of treatment will be determined by comparing the losartan- and placebo-treated groups.
Time frame: 111 minutes to 120 minutes after treatment
Choice accuracy for the stimulus with the high reward probability during the learning phase
During the learning phase accuracies (in percent) for choosing the stimulus with the highest reward probability will be computed. Effects of treatment on choice accuracy in the probabilistic learning task will be examined by comparing accuracies (percent) between the losartan- and placebo-treated group.
Time frame: 90 minutes to 110 minutes after treatment
Learning rate for positive and negative outcomes
The learning rate will be determined by performing computational modelling. The learning rate index for positive and negative outcomes during the learning phase will be compared between the losartan- and placebo-treated group.
Time frame: 90 minutes to 110 minutes after treatment
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Choice accuracy during the learning transfer phase
Following the initial learning phase subjects learning transfer will be examined by asking subjects to choose between stimuli with high versus low reward probabilities. For the transfer phase the choice accuracy for selecting stimuli with the highest reward probability and avoiding stimuli with the lowest reward probability will be computed. The effects of treatment will be determined by comparing the accuracy between the losartan- and placebo-treated groups.
Time frame: 111 minutes to 120 minutes after treatment