Dopaminergic Vulnerability in Long COVID: Why Dopamine May Be the Missing Link Between the Brain and the Body

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Understanding the New eBioMedicine Editorial

A recent editorial published in eBioMedicine, "Dopaminergic Vulnerability in Long COVID: Striatal PET Imaging at the Brain–Body Interface," highlights an emerging area of neuroscience that may fundamentally change how researchers understand Long COVID. The editorial discusses growing evidence that the dopaminergic system—the network of neurons responsible for producing and regulating dopamine—may be particularly vulnerable following SARS-CoV-2 infection.

For millions of people living with Long COVID, symptoms such as profound fatigue, brain fog, poor concentration, depression, reduced motivation, autonomic dysfunction, movement abnormalities, and exercise intolerance have often appeared disconnected. However, the dopaminergic system provides a possible biological explanation that links many of these symptoms into a single neurological framework.

Rather than suggesting that Long COVID is simply a disorder of one organ, this research supports the concept that it affects communication between the brain and the body. Dopamine sits at the center of this communication network.

What Is Dopamine?

Dopamine is a neurotransmitter and neurohormone belonging to the catecholamine family. Although dopaminergic neurons account for less than one percent of all neurons in the brain, they influence virtually every major neurological system.

Dopamine regulates:

  • Motivation
  • Reward and pleasure
  • Learning
  • Attention
  • Working memory
  • Executive function
  • Movement
  • Hormonal regulation
  • Autonomic nervous system activity
  • Stress adaptation

Without sufficient dopamine, the brain loses much of its ability to efficiently process information, initiate movement, sustain motivation, and regulate multiple physiological systems.

Dopamine: More Than the "Feel-Good" Chemical

Dopamine is frequently described as the brain's "feel-good chemical," but this description greatly understates its importance.

Its primary function is not simply producing pleasure—it teaches the brain what is important.

Every time we learn a new skill, accomplish a task, solve a problem, or anticipate a reward, dopamine strengthens the neural pathways responsible for that behavior.

Without dopamine, motivation collapses.

Activities that once felt rewarding become emotionally flat.

Tasks that previously required little effort suddenly become mentally exhausting.

This explains why individuals with dopamine deficiency often describe feeling as though "their brain has run out of fuel."

Dopamine and the Brain's Reward System

The reward system evolved to reinforce behaviors necessary for survival.

Dopamine is released during:

  • Learning
  • Social interaction
  • Exercise
  • Eating
  • Curiosity
  • Goal completion
  • Positive anticipation

Importantly, dopamine is more strongly associated with wanting than with liking.

It generates the motivation to pursue goals before the reward is received.

When dopamine signaling is disrupted, individuals often experience:

  • Loss of drive
  • Reduced initiative
  • Emotional flatness
  • Difficulty beginning tasks
  • Reduced resilience
  • Lack of interest in previously enjoyable activities

These symptoms are commonly reported in Long COVID.

Dopamine and Motor Control

One of dopamine's most critical roles is regulating voluntary movement.

This occurs primarily through the nigrostriatal pathway, where neurons from the substantia nigra project into the basal ganglia.

The basal ganglia function as the brain's movement control center.

Rather than initiating movement directly, they fine-tune movement by regulating:

  • Muscle tone
  • Movement speed
  • Balance
  • Coordination
  • Automatic movements
  • Motor learning

Loss of dopamine disrupts this system, producing:

  • Muscle rigidity
  • Tremor
  • Bradykinesia (slowed movement)
  • Poor balance
  • Loss of dexterity
  • Reduced facial expression

These features are characteristic of Parkinson's disease, which results from progressive degeneration of dopamine-producing neurons.

Some Long COVID patients report subtle Parkinsonian features, although current evidence does not indicate that Long COVID causes Parkinson's disease in most people. Instead, researchers are investigating whether viral infection may temporarily impair dopaminergic function or increase vulnerability in susceptible individuals.

Dopamine and Cognition

Dopamine is equally essential for higher cognitive function.

Within the prefrontal cortex it regulates:

  • Attention
  • Working memory
  • Planning
  • Decision-making
  • Cognitive flexibility
  • Task switching
  • Inhibitory control

Insufficient dopamine leads to:

  • Brain fog
  • Poor concentration
  • Distractibility
  • Mental fatigue
  • Slowed thinking
  • Memory lapses

These symptoms overlap remarkably with those reported in Long COVID.

Where Is Dopamine Produced?

Although dopamine acts throughout the nervous system, it is synthesized in only a handful of specialized locations.

Brain Production

Substantia Nigra

Located in the midbrain, the substantia nigra contains the highest concentration of dopamine-producing neurons.

Its projections regulate:

  • Movement
  • Balance
  • Motor coordination

Loss of neurons here causes Parkinson's disease.

Ventral Tegmental Area (VTA)

The VTA forms the foundation of the brain's reward circuitry.

It projects dopamine to:

  • Limbic system
  • Nucleus accumbens
  • Amygdala
  • Hippocampus
  • Prefrontal cortex

This pathway regulates:

  • Motivation
  • Learning
  • Addiction
  • Emotional processing
  • Goal-directed behavior

Hypothalamus

The hypothalamus produces dopamine primarily as a neurohormone.

Rather than influencing movement, hypothalamic dopamine regulates the endocrine system, particularly by suppressing prolactin release from the pituitary gland.

Dopamine Production Outside the Brain

Dopamine is also synthesized throughout the body.

Adrenal Glands

The adrenal medulla produces dopamine alongside:

  • Epinephrine
  • Norepinephrine

These catecholamines coordinate the body's acute stress response.

Gastrointestinal Tract

The enteric nervous system manufactures substantial amounts of dopamine.

Within the digestive tract it regulates:

  • Intestinal motility
  • Blood flow
  • Mucosal protection
  • Local immune responses

This gut dopamine remains largely separate from brain dopamine because dopamine itself does not readily cross the blood-brain barrier.

Kidneys

Renal dopamine regulates:

  • Sodium excretion
  • Blood pressure
  • Urine production
  • Kidney blood flow

This locally produced dopamine is essential for maintaining fluid and electrolyte balance.

Dopamine and Hormone Regulation

Dopamine also functions as an endocrine regulator.

Its principal hormonal action occurs in the hypothalamic-pituitary axis, where it suppresses prolactin secretion.

Without adequate dopamine:

  • Prolactin rises
  • Menstrual disturbances may occur
  • Fertility may decline
  • Lactation may occur outside pregnancy
  • Sexual dysfunction can develop

Thus dopamine influences reproduction in addition to neurological function.

What Happens When Dopamine Levels Become Too Low?

Because dopamine participates in so many neural circuits, deficiency affects nearly every aspect of brain function.

Psychological Symptoms

People with low dopamine frequently experience:

  • Avolition
  • Loss of motivation
  • Emotional numbness
  • Anhedonia
  • Depression
  • Reduced curiosity
  • Reduced resilience

Even simple daily activities may become mentally overwhelming.

Cognitive Symptoms

Low dopamine contributes to:

  • Brain fog
  • Poor concentration
  • Reduced working memory
  • Slowed thinking
  • Difficulty multitasking
  • Mental fatigue

These symptoms closely resemble the executive dysfunction described by many individuals living with Long COVID.

Physical Symptoms

Deficiency may produce:

  • Chronic fatigue
  • Heavy limbs
  • Muscle stiffness
  • Resting tremor
  • Slowed walking
  • Poor balance
  • Loss of dexterity
  • Chronic constipation
  • Restless legs syndrome

Disorders Associated With Dopamine Dysfunction

Brainimaging of dopamine allows researchers to visualize and measure how this neurotransmitter is released, transported, and bound to receptors across various neural pathways. Scientists primarily use Positron Emission Tomography (PET) and functional MRI (fMRI) to track these complex interactions in the living human brain.

Several neurological and psychiatric disorders arise from abnormal dopamine signaling.

These include:

  • Parkinson's disease
  • ADHD
  • Restless legs syndrome
  • Major depressive disorder
  • Substance dependence
  • Certain movement disorders
  • Hyperprolactinemia

Each involves different dopamine pathways rather than a single "low dopamine" state.

Brain imaging of dopamine allows researchers to visualize and measure how this neurotransmitter is released, transported, and bound to receptors across various neural pathways. Scientists primarily use Positron Emission Tomography (PET) and functional MRI (fMRI) to track these complex interactions in the living human brain.

What Happens When Dopamine Is Too High?

Excess dopamine can be equally disruptive.

Causes include:

  • Dopamine agonist medications
  • Stimulants
  • Certain neurological disorders
  • Mania associated with bipolar disorder

Symptoms may include:

  • Severe insomnia
  • Hyperactivity
  • Restlessness
  • Racing thoughts
  • Elevated heart rate
  • High blood pressure
  • Excessive sweating
  • Muscle tics
  • Reduced appetite
  • Dyskinesia in patients receiving excessive levodopa

Healthy brain function depends on balanced dopamine signaling rather than simply maximizing dopamine levels.

Dopamine and Long COVID

One of the most intriguing aspects of the eBioMedicine editorial is its focus on the striatum, a dopamine-rich brain region responsible for integrating movement, cognition, motivation, and autonomic regulation.

Advanced PET imaging suggests that some individuals with Long COVID exhibit abnormalities consistent with altered dopaminergic function.

Researchers propose several mechanisms that may contribute to this vulnerability:

  • Persistent neuroinflammation
  • Microglial activation
  • Oxidative stress
  • Mitochondrial dysfunction
  • Cerebral hypoperfusion
  • Endothelial dysfunction
  • Disruption of the blood-brain interface
  • Immune-mediated injury to dopaminergic pathways

These mechanisms remain under investigation, and PET imaging findings do not yet establish that all Long COVID symptoms are caused by dopamine deficiency. However, they provide a compelling biological framework that helps explain why neurological, autonomic, cognitive, and motor symptoms often occur together.

The Brain–Body Interface

One of the editorial's central concepts is the brain-body interface.

Dopamine links the central nervous system with:

  • The autonomic nervous system
  • The endocrine system
  • Immune regulation
  • Gastrointestinal function
  • Cardiovascular control
  • Stress physiology

Disruption within this network could explain why Long COVID affects multiple organ systems simultaneously rather than producing isolated neurological symptoms.

This systems-based perspective aligns with growing evidence that Long COVID is a complex neuroimmune disorder involving continuous communication between the brain and peripheral organs.

Dopamine and Cushing's Syndrome

Dopamine also has important implications in endocrine disease, particularly Cushing's syndrome.

Cushing's syndrome results from excessive cortisol production, often driven by ACTH-secreting pituitary tumors.

Many of these tumors express dopamine D2 receptors.

Because of this, dopamine agonists such as cabergoline can suppress ACTH secretion, lower cortisol production, and, in some patients, reduce tumor growth.

In healthy physiology, dopamine helps regulate the hypothalamic-pituitary-adrenal (HPA) axis by modulating stress hormone release. In Cushing's syndrome, autonomous tumor activity overrides these normal feedback mechanisms, which is why pharmacologic dopamine receptor stimulation may partially restore hormonal control.

Combined Effects

Because cortisol helps regulate dopamine activity in the brain, having both levels drop creates a compounding downward spiral:

In addition, low cortisol and low dopamine can severely reduce energy, motivation, and emotional resilience. Cortisol deficiency limits the body's ability to meet physical and mental demands, while low dopamine removes the motivation and reward needed to push through challenges. This creates a "wired but tired" state—feeling exhausted yet unable to function effectively. Together, these deficiencies can cause profound fatigue, chronic apathy, poor stress tolerance, and increase the risk of depression and anxiety due to impaired mood regulation.

Looking Ahead

The emerging evidence surrounding dopamine and Long COVID represents an important shift in understanding the disease.

Rather than viewing symptoms such as fatigue, brain fog, dysautonomia, depression, movement abnormalities, and cognitive dysfunction as unrelated complaints, researchers are increasingly investigating whether they may reflect disruption of interconnected dopaminergic networks that span the brain and body.

Although more research is needed before dopaminergic imaging or therapies become part of routine clinical practice, the findings highlighted in eBioMedicine provide a strong scientific rationale for studying dopamine as a central component of Long COVID biology.

Future investigations combining PET imaging, biomarkers of neuroinflammation, autonomic testing, and clinical outcomes may clarify which patients have dopaminergic dysfunction, how these abnormalities develop after SARS-CoV-2 infection, and whether targeted therapies can improve recovery.

Understanding dopamine is therefore not only essential for explaining movement, motivation, and cognition—it may also prove critical in unraveling one of the most complex post-viral illnesses of the modern era.

References:

Images of dopamine pathways
https://www.shutterstock.com/search/dopamine-pathways?dd_referrer=https%3A%2F%2Fwww.google.com%2F

Dopamine: The pathway to pleasure
https://www.health.harvard.edu/mind-and-mood/dopamine-the-pathway-to-pleasure

What is Dopamine?
https://www.news-medical.net/health/What-is-Dopamine.aspx

Dopamine - Neurotransmitter
https://parisbraininstitute.org/glossary/dopamine

The chemical tools for imaging dopamine release
https://www.sciencedirect.com/science/article/pii/S2451945621001604 

Dopamine
https://my.clevelandclinic.org/health/articles/22581-dopamine

The chemical tools for imaging dopamine release
https://www.sciencedirect.com/science/article/pii/S2451945621001604

Dopamine
https://www.cell.com/current-biology/fulltext/S0960-9822(22)01022-3

Medical Treatment in Cushing’s Syndrome: Dopamine Agonists and Cabergoline
https://karger.com/nen/article-abstract/92/Suppl.%201/116/226723/Medical-Treatment-in-Cushing-s-Syndrome-Dopamine?redirectedFrom=fulltext

What are the symptoms of high dopamine in females?
https://www.anfacademy.com/what-are-the-symptoms-of-high-dopamine-in-females/

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9   

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