The Role of Dopaminergic and Noradrenergic Neurotransmission in Value- and Salience-based Decision-Making

NCT04371146 | Completed DMC

• 1 other identifier: Value-Salience-2017-0444
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Approach versus avoidance decisions are at the centre of adaptive behaviour and survival. These decisions are thought to be guided by the value of the choice options, which are a function of the magnitude of predicted rewards and punishments. Moreover, the allocation of attention to choice options is thought to be driven by salience, i.e. the overall importance of the predicted outcomes. While salience increases with the magnitude of both predicted rewards and predicted punishments, value increases with reward but decreases with punishment. In previous research, value and salience have often remained confounded during value-based decision making. Rodent research suggests that value is associated with dopamine and salience with norepinephrine. The present study aims at disentangling value from salience processing during decision-making tasks in healthy subjects by administering dopamine or noradrenaline reuptake inhibitors. This is done by using a single dose challenge in a randomized placebo-controlled between subject's design, administering either methylphenidate (35 mg), reboxetine (8 mg), or placebo to healthy young participants before they perform tasks tapping into various aspects of value and salience.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Response time data

  The investigators record responses and specifically reaction times during 5 different decision-making tasks. In a value vs salience task, value and salience processing is disentangled during value-based decision-making. Participants either accept or reject compound stimuli that were before associated with monetary outcomes. In a face in the crowd task, participants detect a target face (angry vs happy) in a crowd of opposite face type. During a task on risk and ambiguity decision-making, participants have to decide between safe and lottery options associated with either monetary risk or ambiguity. In an adaptive risk-taking task, participants have to choose between two risky monetary options. In an effort task, participants decide whether they are willing to exert physical effort for monetary reward. Response times are measured in milliseconds from the tasks. The investigators calculate how long participants take to make decisions in each trial.

  These tasks take place 1,5 hours after the drug was administered

• Choice data

  As a dependent variable the investigators record responses and specifically choices made during the above-mentioned different decision-making tasks. The investigators evaluate what kind of answers were made during each trial of the decision-making tasks, in respect to correctness or preference (percentage).

  These tasks take place 1,5 hours after the drug was administered

Secondary Outcomes (2)

• Computational modelling applied to choice data

  These tasks take place 1,5 hours after the drug was administered

• Computational modelling applied to response time data

  These tasks take place 1,5 hours after the drug was administered

Study Arms (3)

Dopamine reuptake inhibitor

EXPERIMENTAL

Participants in the dopamine reuptake inhibitor group will be asked to take one pill containing 35 mg methylphenidate 1.5 hours before performing the tasks.

Drug: Methylphenidate

Noradrenaline reuptake inhibitor

EXPERIMENTAL

Participants in the noradrenaline reuptake inhibitor group will be asked to take one pill containing 8 mg reboxetine 1.5 hours before performing the tasks.

Drug: Reboxetine

Placebo

PLACEBO COMPARATOR

Participants in the placebo group will be asked to take a placebo pill 1.5 hours before performing the tasks.

Drug: Placebos

Interventions

Methylphenidate DRUG

35 mg methylphenidate (Ritalin®) is administered once using a randomized placebo-controlled between subject's design

Also known as: Ritalin®

Dopamine reuptake inhibitor

Reboxetine DRUG

8 mg Reboxetine (Edronax®) is administered once using a randomized placebo-controlled between subject's design

Also known as: Edronax®

Noradrenaline reuptake inhibitor

Placebos DRUG

A placebo pill is administered once using a randomized placebo-controlled between subject's design

Also known as: Placebo Pill

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Physically and psychiatrically healthy men and women aged ≥ 18- ≤ 35 years
• Ability and willingness to participate in the study
• Signed informed consent

You may not qualify if:

• Serious past brain disease or injury (data quality)
• Frequent headaches (of any sort, \> 1/week) or migraine (irrespective of frequency)
• History of epileptic seizures
• Any neurological disorder
• Surgery to head or heart (safety, potential metal pieces)
• Pacemaker, hearing aid or neurostimulator (safety, metal pieces)
• Known cardiac or cardiovascular disease or anomaly
• Family history of sudden death due to cardiac arrhythmia
• High or low blood pressure, history of heart attack, infrequent heartbeat
• Respiratory problems (including difficulty with breathing through the nose)
• Glaucoma (present or in history)
• Insufficiency of kidney or liver, acute liver disease
• Any psychiatric disorder (especially depression, mania, schizophrenia, addiction and suicidality)
• Severe vocal or motor tics (methylphenidate, data quality)
• Severe psychosomatic disorder (somatic complaints without clear medical cause, has a mental component)

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University of Zurich

Zurich, 8006, Switzerland

Location

MeSH Terms

Interventions

Methylphenidate; Reboxetine

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines

Study Officials

• Philippe Tobler, PhD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: All participants will receive the same instructions, and neither the participants nor the experimenters are informed which drug is used. Participants must take the drug in front of the investigator, to ensure correct intake and compliance.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The investigators implement a randomized, double-blind, placebo-controlled between-subjects design, using one factor (pharmacological intervention) with three levels (reboxetine, methylphenidate and placebo).

Study Record Dates

• First Submitted: April 26, 2020
• First Posted: May 1, 2020
• Study Start: July 3, 2019
• Primary Completion: February 13, 2020
• Study Completion: February 13, 2020
• Last Updated: May 1, 2020

Record last verified: 2020-04

Locations

CH (1)