The Role of Dopamine, Reward Learning and Prefrontal Activity in Expectation-induced Mood Enhancement

Summary

Although placebo effects on depressive symptoms are well documented, the underlying mechanisms and moderating factors of expectation effects on mood and depression are poorly understood. Various studies show reduced reward processing in clinical and subclinical depression, presumably due to abnormalities in the dopamine (DA) system. Here, the investigators will test whether expectation-induced mood enhancement is mediated by endogenous DA activity and reward learning, and moderated by individual differences in depression-related personality traits. Healthy participants (N=296) will be tested for potentially relevant personality traits and given an inactive substance (placebo) or a DA D2-receptor antagonist sulpiride (400 mg) in combination with a low vs. high expectation manipulation (fully crossed 2x2 placebo design) before performing a probabilistic reinforcement learning task, an effort expenditure task, and undergo a depressed mood induction procedure. Further, EEG indices will be assessed throughout the tasks.

The investigators expect that positive expectation improves participants' reinforcement learning, increases participants' willingness to make effort in order to obtain reward, and leads to less depressive symptoms as indicated by mood ratings upon depressive mood induction. If the overall effect of positive expectations is mediated by DA, high-dose sulpiride should block expectation-induced effects, i.e., the anticipated enhanced reinforcement learning and effort expenditure as well as mood improvement in the high vs. low expectation group.

Conditions

• Placebo Effect on Mood Improvement

Interventions

DRUG

Sulpiride 400 MG

The substituted benzamide sulpiride is a selective D2-receptor antagonist that is generally well tolerated and has a low affinity to histaminergic, cholinergic, serotonergic, adrenergic, or GABA receptors. Sulpiride is slowly absorbed from the gastrointestinal tract and peak serum levels occur at 3 hours . In low doses (50-200 mg), sulpiride presumably blocks presynaptic autoreceptors, thereby elevating DA levels and reducing depressive symptoms, whereas higher doses lead to a predominant blockade of postsynaptic receptors. The dose in the present study (400 mg) is sufficient for behaviorally relevant modulations of dopaminergic processing with minimal risk of side effects. Note that participants in the sulpiride group actually receive a dose that is presumably too high to produce antidepressant effects.

DRUG

Placebo

Participants receive an inactive placebo capsule.

BEHAVIORAL

High expectation manipulation

Participants will be told by the study clinicians that an antidepressive sulpiride capsule is administrated.

BEHAVIORAL

Low expectation manipulation

Participants will be told by the study clinicians that an inactive placebo capsule is administrated.

Sponsors & Collaborators

• Philipps University Marburg

  lead OTHER

Principal Investigators

• Erik M Mueller, Prof. Dr. · Philipps University Marburg

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-12-09

Primary Completion

2023-09-22

Completion

2023-09-22

Countries

• Germany

Study Locations