The Effects of Losartan on Reward Reinforcement Learning

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Role of the Renin-angiotensin System in Reward Reinforcement Learning

Conditions
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Healthy

Intervention / Treatment
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* Drug: Losartan
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects without past or current psychiatric or neurological disorders Right-handedness Normal or corrected-normal version Exclusion Criteria: History of head injury Medical or psychiatric illness Hypertension General cardio-vascular alteration or diseases Allergy against medications Visual or motor impairments Claustrophobia Drug addiction Nicotine dependence FMRI contradictions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Losartan group<br>Drug: Losartan | Drug: Losartan<br>* administration of losartan (50 mg) (oral)<br>* Other names: Cozaar Oral Tablet;|
| Placebo Comparator: Placebo group<br>Drug: Placebo Oral Tablet | Drug: Placebo oral tablet<br>* administration of placebo (oral)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD-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. | 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. | 111 minutes to 120 minutes after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 90 minutes to 110 minutes after treatment | 
| 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. | 111 minutes to 120 minutes after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Losartan, Reward reinforcement learning