Learning and Decision-making

Study Overview
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Brief Summary
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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.

Official Title
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How Does the Brain Learn About Positive and Negative Things?

Conditions
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Motivation

Intervention / Treatment
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* Drug: placebo
* Drug: haloperidol 2mg
* Drug: propranolol 40mg


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Placebo Comparator: HV/Placebo<br>Oral placebo (tablet) | Drug: placebo<br>* oral formulation<br>|
| Active Comparator: HV/Haloperidol<br>2mg (oral) | Drug: haloperidol 2mg<br>* oral formulation<br>|
| Active Comparator: HV/Propranolol<br>40mg (oral) | Drug: propranolol 40mg<br>* oral formulation<br>|

What is the study measuring?
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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 |