The Effects of Losartan on Reward Reinforcement Learning

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

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.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: Losartan; Drug: Placebo oral tablet

Detailed Description

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
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 611731
      • Recruiting
      • University of Electronic Science and Technology of China
      • Contact: Weihua Zhao, PhD; Email: zarazhao.uestc@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Losartan group; Drug: Losartan	Drug: Losartan; administration of losartan (50 mg) (oral); Other Names: Cozaar Oral Tablet
Placebo Comparator: Placebo group; Drug: Placebo Oral Tablet	Drug: Placebo oral tablet; administration of placebo (oral)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Electronic Science and Technology of China
• Investigators: Principal Investigator: Benjamin Becker, PhD, University of Electronic Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Losartan; Reward reinforcement learning
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: UESTC-neuSCAN-75

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No