Clinical trial NCT04371146: The Role of Dopaminergic and Noradrenergic Neurotransmission in Value- and Salience-based Decision-Making
Official title: The Role of Dopaminergic and Noradrenergic Neurotransmission in Value- and Salience-based Decision-Making
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2020-05-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators implement a randomized, double-blind, placebo-controlled between-subjects design, using one factor (pharmacological intervention) with three levels (reboxetine, methylphenidate and placebo).
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Response time data
timeFrame: These tasks take place 1,5 hours after the drug was administered
measure: Choice data
timeFrame: These tasks take place 1,5 hours after the drug was administered
Secondary outcomes:
measure: Computational modelling applied to choice data
timeFrame: These tasks take place 1,5 hours after the drug was administered
measure: Computational modelling applied to response time data
timeFrame: These tasks take place 1,5 hours after the drug was administered
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University of Zurich
Study officials:
affiliation: University of Zurich
name: Philippe Tobler, PhD
role: PRINCIPAL_INVESTIGATOR
References: