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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Losartan group | Experimental | Drug: Losartan |
|
| Placebo group | Placebo Comparator | Drug: Placebo Oral Tablet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan | Drug | administration of losartan (50 mg) (oral) |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weihua Zhao, PhD | Contact | 86-28-61830811 | zarazhao.uestc@outlook.com |
| Name | Affiliation | Role |
|---|---|---|
| Benjamin Becker, PhD | University of Electronic Science and Technology of China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Electronic Science and Technology of China | Recruiting | Chengdu | Sichuan | 611731 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36810437 | Derived | Xu T, Zhou X, Kanen JW, Wang L, Li J, Chen Z, Zhang R, Jiao G, Zhou F, Zhao W, Yao S, Becker B. Angiotensin blockade enhances motivational reward learning via enhancing striatal prediction error signaling and frontostriatal communication. Mol Psychiatry. 2023 Apr;28(4):1692-1702. doi: 10.1038/s41380-023-02001-6. Epub 2023 Feb 21. |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo oral tablet | Drug | administration of placebo (oral) |
|
| 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 |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |