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

University of Zurich (UZH)

Status: Completed

Conditions: Healthy

Treatments: Drug: Placebos; Drug: Reboxetine; Drug: Methylphenidate

Study type: Interventional

Funder types: Other

Identifiers

NCT04371146

Value-Salience-2017-0444

Details and patient eligibility

About

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.

Enrollment: 120 patients

Sex: All

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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)
• Pregnancy, nursing, or currently planned pregnancy
• Current allergy in general or allergy to methylphenidate or reboxetine
• Severe intolerance to lactose including strong diarrhea after only a few mg (weak lactose intolerance is no exclusion criterion as medication only contains slightest dosage (around 4mg) of lactose)
• Currently taking any medication that might interfere with Methylphenidate and Reboxetine, especially MAO-Inhibitors (e.g. Aurorix (Moclobemid) und Azilect (Rasagilin), antipsychotics, antibiotics, and medication for heart diseases
• Currently taking any further medication (besides birth control) or natural products (infrequent intake of natural products and/or food supplements need to be mentioned to the examiner)
• Drug abuse (current or past abuse; in case of single use please inform the examiner)
• Serious acute or chronic disease that could interfere with participation in the experiments
• Inability to understand the instructions or insufficient comprehension of German language
• Participants having their weight outside of the range of ≥ 60 kg - ≤ 80 kg
• Clinically relevant score in STAI T (anxiety), measured during prescreening on a separate day
• Long QT syndrome or other arrhythmias, measured during prescreening on a separate day

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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120 participants in 3 patient groups, including a placebo group

Dopamine reuptake inhibitor

Experimental group

Description:

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.

Treatment:

Drug: Methylphenidate

Noradrenaline reuptake inhibitor

Experimental group

Description:

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.

Treatment:

Drug: Reboxetine

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebos