Learning and Decision-making

How Does the Brain Learn About Positive and Negative Things?

A fundamental aspect of daily life decision-making involves the evaluation of costs and benefits. Neural systems underlying cost-benefit evaluation have been extensively examined, but the specific role of different neurotransmitters remains unclear. Numerous studies suggest that both dopamine (DA) and norepinephrine (NE) are closely related to reinforcement learning, guided exploration/exploitation, and behavioural energisation, although no studies to date have investigated the distinct role of DA and NE on cost-benefit decision-making and learning in human subjects.

Study Overview

• Status: Completed
• Conditions: Motivation
• Intervention / Treatment: Drug: placebo; Drug: haloperidol 2mg; Drug: propranolol 40mg

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willingness to sign an informed consent
• Age between 18 and 35
• Body-Mass Index (BMI) between 17.5-30
• Availability for participation through the duration of the study

Exclusion Criteria:

• Diagnosis of a psychiatric or neurological disorder, including substance abuse or dependence (yes/no self-report - lifetime)
• Use of any psychopharmacological treatment 3 weeks before the test day (yes/no self-report)
• Use of any blood pressure medication (yes/no self-report - lifetime)
• Pregnancy (confirmed via urine pregnancy test) or nursing (yes/no self-report) or have plans to get pregnant in the near future (yes/no self-report) (females only)
• Diagnosis of a cardiac disease (medical questionnaire), obstructive respiratory disease (medical questionnaire), abnormal blood pressure (diastolic< 60mmHg; systolic< 90mmHg) (medical screening)
• Chronic renal failure (medical questionnaire)
• Hypothyroidism (medical questionnaire)
• Diabetes (medical questionnaire)
• Hypersensitivity to phenothiazines (medical questionnaire)
• Diagnosis of a cardiac disease (medical questionnaire)
• Alcohol consumption in the 24 hours before the test session starts (yes/no self-report)
• Food intake less than 3 hours before the test day (yes/no self-report)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: HV/Placebo; Oral placebo (tablet)	Drug: placebo; oral formulation
Active Comparator: HV/Haloperidol; 2mg (oral)	Drug: haloperidol 2mg; oral formulation
Active Comparator: HV/Propranolol; 40mg (oral)	Drug: propranolol 40mg; oral formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-benefit reinforcement learning performance	2-choice reinforcement learning task (based on Voulgaropoulou et al., 2021 PNEC)	~ 2.5 hours post-drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effort-based decision-making	motivation to acquire rewards (e.g., Reddy et al. 2015)	~ 2 hours post-drug administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiology I	Heart rate	pre, +30 min., +60 min., +90 min., +120 min., +190 min. post-drug administration
Physiology II	blood pressure	pre, +30 min., +60 min., +90 min., +120 min., +190 min. post-drug administration

Collaborators and Investigators

• Sponsor: Maastricht University

Publications and helpful links

General Publications

• Voulgaropoulou SD, Fauzani F, Pfirrmann J, Vingerhoets C, van Amelsvoort T, Hernaus D. Asymmetric effects of acute stress on cost and benefit learning. Psychoneuroendocrinology. 2022 Apr;138:105646. doi: 10.1016/j.psyneuen.2021.105646. Epub 2021 Dec 24.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): April 30, 2023
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: August 23, 2023
• First Posted (Actual): August 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Anti-Dyskinesia Agents; Propranolol; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: DANE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No