One of the most critical neurotransmitters in the brain is dopamine. It is best known for its reward, motivation, and pleasure functions. It helps control of focus, motivation, cognitive flexibility, and emotional resilience.
Dopamine is one of the primary regulators of motor control and coordination of body movements, in addition to these creative-productive capacities and states.
Dopaminergic substances and actions influence dopamine-related brain activity. The dopaminergic system’s proper operation is critical for cognitive performance and emotional motivation.
Let’s break down the dopaminergic system, including what dopamine is, where and how it is metabolized, and how it can be supported.
What Is Dopamine and How Does It Work?
Dopamine is one of the catecholamine family’s three main signaling molecules. The other two are the fight-or-flight response molecules epinephrine (adrenaline) and norepinephrine (norepinephrine) (noradrenaline).
Dopamine is a neurotransmitter that is produced in the brain. It’s also produced by and used by other body systems, where it serves as an essential chemical messenger.
Dopamine affects the heart by modulating cardiovascular function, stimulating heart muscle contraction, and encouraging the widening of blood vessels required for proper blood flow.
Dopamine is a neurotransmitter that helps the kidneys function correctly by increasing urination and excreting excess sodium (salt).
Dopamine also affects the immune system and lymphocyte activity (a type of white blood cell that aids in the immune system’s ability to protect us).
“Dopamine neurons are relatively few in number—only 1 percent of brain neurons are dopaminergic—but have a big impact on creative-productive capacities, emotions, and coordination of body movements.”
The brain must allow certain things in (such as nutrients) and out (such as metabolic waste products) while also protecting itself from other things (like bacteria).
It accomplishes this through the blood-brain barrier, which serves as a sort of doorman, deciding who gets in and who doesn’t.
Dopamine is a neurotransmitter that does not cross the blood-brain barrier. As a result, all dopamine in the brain must be produced locally in dopaminergic nerve cells (neurons) from dopamine building block molecules. Only about 1% of brain neurons are dopaminergic, even though dopamine promotes many critical brain capacities and states.
If we want to achieve and maintain peak brain performance throughout our lives, we must protect and support these few neurons.
To function correctly, we need a sufficient amount of dopamine.
Where Is Dopamine Produced In The Brain? What Is It Used For? What Exactly Does It Do?
Dopaminergic neurons are restricted to a few small but not insignificant brain areas. This isn’t to say that dopamine’s effects are limited to these areas of the brain. The nerve fibers (axons) that connect dopaminergic neurons to other neurons are called axons.
Dopamine-related information is transmitted to neurons in other parts of the brain via these nerve fibers. Dopamine exerts its modulatory effects elsewhere in the brain via these axons.
The midbrain, which contains the vast majority of dopaminergic neurons, is the brain’s central dopamine-producing region. The substantia nigra is the most prominent dopaminergic cluster of neurons in the midbrain. It plays a crucial role in the regulation of movement and reflexes.
Another important dopaminergic area in the midbrain is the ventral tegmental area (VTA).
Another major dopaminergic pathway in the brain is the mesolimbic dopaminergic pathway, which has projections to the nucleus accumbens, olfactory tubercle, amygdala, and hippocampus.
This pathway, also called the reward pathway, is involved in reward, the motivational component of reward-motivated behavior, behavioral reinforcement, and pleasure perception. Reward processes (i.e., wanting and liking, and the reinforcement of pleasure behaviors),
Executive functions (i.e., goal-directed behavior, cognitive flexibility, and problem-solving,
Associative learning (i.e., acquiring and modifying behaviors, skills, and so on), and
Motor control are all influenced by dopaminergic pathways in the brain”
“The mesocortical dopaminergic pathway, which includes projections from the VTA to the prefrontal cortex and cingulate cortex, is a third major brain dopamine pathway involved in cognitive control, behavioural flexibility, and emotional resilience.
Dopamine modulates executive function, which is the set of higher-order cognitive processes that underpin goal-directed behaviors such as impulse control, response inhibition, attention, working memory, cognitive flexibility, planning, judgment, and decision-making, through this pathway.
Important aspects of executive function, such as cognitive flexibility, set-shifting (task-switching), and attention, are mediated by dopaminergic activity in the medial prefrontal cortex.
The optimal performance of these processes is linked to higher levels of dopamine.
Dopamine, serotonin, glutamate, GABA, acetylcholine, and other neurotransmitters are chemical messengers that carry information from one neuron (message sender) to another neuron (target) (message recipient).
A synapse is a small gap between two neurons.
Note: It is estimated that an adult human brain contains 100–500 trillion synapses!
Dopamine message-receiving neurons have receptors that listen for and watch for dopamine messages (think of them as the neuron’s eyes or ears).
When dopamine receptors detect it, they are activated, resulting in either excitation (turning on) or inhibition (turning off), depending on the type of dopamine receptors on the target neuron. While this may appear to be a difficult task, keep the following points in mind:
The type of receptors on the target neurons and the amount of dopamine released by the sending neurons will determine how a neuron responds to dopamine.
The dopamine message (i.e., dopamine release and receptor activation) will be brief. Even so, the effects will linger for a long time.
Because dopamine pathways connect to brain areas affecting voluntary and involuntary muscle movements, emotional life, and creative-productive capacities and states, it has significant effects (despite being produced in only small brain areas).
Synthesis, Signaling, and Cleanup of Dopamine
Neurotransmitters share several characteristics. The first is that they are created (or synthesized by neurons.
They are then moved to synaptic vesicles near the ends of neurons, where they are stored until needed.
This happens in preparation for signalling, which entails releasing the neurotransmitter from the message-sending neuron into the space between neurons (synaptic cleft) to activate (i.e. bind to) receptors on message-receiving neurons.
The space between neurons must be cleaned up after this signal is sent to prepare for the next time a message must be sent.
This can be accomplished by either reabsorbing the neurotransmitter for reuse (recycling) or degrading (breaking down) the neurotransmitter.
Let’s look at how these things happen with dopamine.
Because dopamine does not cross the blood-brain barrier, it must be synthesized in the brain from molecules that can enter the brain as building blocks (i.e. precursors). L-phenylalanine, L-tyrosine, and L-DOPA are three key precursor molecules in the dopamine synthesis pathway that can enter the brain.
These molecules can be used to make dopamine, and the molecules enter the pathway at different points. The essential (i.e., required) amino acid L-phenylalanine is the most fundamental of the three building blocks.
Essential amino acids are not produced by the body and must be obtained through the diet.
The next step in the dopamine pathway is L-tyrosine. It is considered conditionally (i.e., circumstantially) essential because it can be synthesized from L-phenylalanine. Because it can be synthesized in the body, it isn’t considered essential in the same way that L-phenylalanine is.
However, there are times when the body may not meet demands (e.g., illness, high stress, increased cognitive demands).
It becomes critical to obtain it through diet under these conditions or circumstances. L-DOPA is the last molecule that can enter the dopamine pathway. So the pathway progresses from L-Phenylalanine to L-Tyrosine to L-DOPA Dopamine, at least in a large picture building block sense.
The slowest step in a metabolic pathway is known as a rate-limiting step. It establishes the overall rate at which the final product will be manufactured. The rate-limiting step is often used as an analogy, with the congested area representing the rate-limiting step. “
Let’s start with the L-tyrosine building block to see how this works.
Dopamine is made from the amino acid L-tyrosine in the nerve terminals and in the cell bodies of dopaminergic neurons (which, as mentioned, can be made from L-phenylalanine).
Tyrosine hydroxylase (T.H.) converts L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which is then converted to dopamine by aromatic-L-amino-acid decarboxylase (AAAD, also known as DOPA decarboxylase [DDC]) with the coenzyme pyridoxal-5′-phosphate (the active form of vitamin B6).]
Note: Enzymes are catalysts that help to catalyze specific biochemical reactions; their names usually end in “ase.”
Coenzymes are components of enzymes. Vitamins are the source of many coenzymes. [
The rate-limiting step (i.e., the slowest step in the pathway, akin to a bottleneck, and the most likely location for a metabolic traffic jam) in the synthesis of dopamine is the synthesis of L-DOPA by tyrosine hydroxylase (T.H.).
Because dopamine is the precursor to the synthesis of the other catecholamine neurotransmitters, norepinephrine, and epinephrine (in noradrenergic and adrenergic neurons, respectively), tyrosine hydroxylase (T.H.) is the limiting enzyme in the synthesis of the three neurotransmitters.
A vesicular monoamine transporter transports dopamine into synaptic vesicles after it is synthesized.
Dopamine is stored in these vesicles until it is released into the synaptic cleft by an action potential triggered by calcium influx.
This transport and storage take place in the message-sending neuron in preparation for future dopamine messages.
The calcium influx initiates the signaling process because it is the biological cue to send the message.
Dopamine binds to and activates either postsynaptic (message-receiving) or presynaptic (message-sending) autoreceptors after it is released.
Dopamine molecules are released from their receptors and taken up into the presynaptic cell or surrounding glial cells by the dopamine transporter (DAT) or the plasma membrane monoamine transporter when an action potential is elicited in the postsynaptic neuron (VMAT).
This is a part of the cleanup process that involves recycling.
Dopamine is either broken down or repackaged into vesicles for future use once it returns to the cell.
To ensure that neurotransmitters do not float around, complex regulatory systems are in place.
As a result, cleanup is critical for effective signaling. Part of the reason for the cleanup is that dopamine is a valuable resource that should not be squandered.
It’s also due to the way signaling works.Change is the foundation of signalling.
It’s not the quantity of something that causes a reaction; it’s the change in quantity.
The analogy of light is useful. You’d notice the difference if you lit a single candle in a dark room.
You might not if you lit one more candle in a room with a hundred other candles lit. Neurotransmitters work on the principle of relative change.
Responses are elicited by short bursts of dopamine release. However, the space between neurons must be the equivalent of a dark room, not already brightly lit by dopamine candles, for the best response to occur with the smallest amount of dopamine.
For recycling and degradation, multiple enzymes work together in the dopamine cleanup pathways.
Rhese will be discussed briefly below. The important thing to remember is that promoting dopamine signaling also entails promoting these enzymes (as a reminder, enzymes have names that end in “ase”).
Monoamine oxidase degrades dopamine into inactive metabolites within the cell (MAO). MAO catalyzes the oxidative deamination of dopamine to produce DOPAL, which is then converted to DOPAC by aldehyde dehydrogenase (ALDH) and then to homovanillic acid (HVA) by catechol-O-methyltransferase, the primary metabolite of dopamine (COMT). MAO-A and MAO-B, two isozymes of MAO, are found on the outer membrane of mitochondria.
Dopamine can be metabolized by both isoforms. MAO-A is found primarily in catecholaminergic neurons, while MAO-B is found primarily in glial cells (and serotonergic and histaminergic neurons).
In brain regions with low expression of the presynaptic dopamine transporter, COMT-dependent extracellular dopamine inactivation is critical.
This recycling mechanism removes dopamine from message-sending neurons and returns it to them for inactivation or reuse.
It’s critical to have this degradation backup plan to inactivate dopamine when the message-sending neurons aren’t designed to take up and recycle it, keeping the space between neurons the equivalent of a dark room for the next time a dopamine burst is sent.
Dopamine Signaling Stack
Critical parts of designing a dopamine stack are:
- Augment the precursor pool of compounds used to make it.
- Give full pathway support.
- Support enzyme functions involved in dopamine synthesis, signaling, and cleanup.
- Promote balanced signaling and neuroprotection.
Let’s Put these pieces together now.
The rate-limiting step in this L-DOPA pathway is the enzyme tyrosine hydroxylase. This is the enzymatic step that turns L-tyrosine into L-DOPA.
Mucuna pruriens, a legume (bean) family member, is included in this stack because it is a natural source of L-DOPA, which can enter the pathway after this step.
We use this herbal ingredient to supply the amount of L-DOPA that a person would consume if they ate about 3-6 ounces of fava beans (fava beans are considered one of the richest food sources of L-DOPA).
This ingredient thereby supports the production of dopamine and bypasses the potential metabolic traffic jam.
While L-DOPA is further along the pathway than L-tyrosine, there’s one more enzymatic step to go to get to dopamine.
Vitamin B6, as Pyridoxal 5’-phosphate (P5P), is included in the stack to support the conversion of L-DOPA to dopamine. * The enzyme DOPA decarboxylase (DDC) is responsible for converting L-DOPA to dopamine. It requires P5P as the coenzyme form of vitamin B6 to exert its function.
With the goal of full pathway support in mind, two amino acid dopamine building blocks are included.
As mentioned, L-tyrosine is a conditionally essential amino acid and the direct precursor to L-DOPA. It is included in this stack in the form of N-Acetyl-L-Tyrosine to augment the supply of L-tyrosine available for L-DOPA (and then dopamine) synthesis.
L-tyrosine is synthesized from the essential amino acid L-phenylalanine by the enzyme phenylalanine hydroxylase.
We include DL-Phenylalanine in the stack to support healthy levels of L-phenylalanine available for L-tyrosine synthesis, furthering our complete pathway support goal.
By including Mucuna pruriens, N-Acetyl-L-Tyrosine, and DL-Phenylalanine, the stack supports three different steps, with different kinetics, of the dopamine synthesis pathway, allowing for a prolonged and sustained availability of precursor resources to be recruited for its synthesis.
Deficiency in any precursor amino acid or any cofactor in the catecholaminergic anabolic pathways can impair the synthesis of all three catecholamine neurotransmitters.
Both tyrosine hydroxylase (i.e., T.H. is the enzyme that makes L-DOPA from L-tyrosine) and phenylalanine hydroxylase (i.e., PAH is the enzyme that makes L-tyrosine from L-phenylalanine) require tetrahydrobiopterin as a coenzyme.
Although uridine may decrease the density of dopamine receptors, it seems to enhance their signal transduction and turnover rate, leading to an increase in dopamine-dependent behaviors.
In other words, it may promote improved results on the message-receiving side (listening end) of the dopamine signaling process.
Uridine Monophosphate also enhances potassium-evoked dopamine release.
Uridine Monophosphate has a unique role in the dopamine stack.
Although uridine may decrease the density of dopamine receptors, it seems to enhance their signal transduction and turnover rate, leading to an increase in dopamine-dependent behaviors.
In other words, it may promote improved results on the message-receiving side (listening end) of the dopamine signaling process. * Uridine Monophosphate also enhances potassium-evoked dopamine release.
Why Should You Support Dopaminergic Pathways and Processes?
Dopamine modulates a wide array of cognitive capacities and emotional states. But what happens if demands for dopamine signaling exceed supplies? Or if there are obstacles interfering with or slowing dopamine creation, signaling, or cleanup processes?
The goal is not to try to control the dopamine system. Instead, using a complexity science approach, the goal is to provide resources, support regulatory functions and dopamine levels at multiple points along the interconnected pathways (especially points where there’s likely to be a metabolic traffic jam), and allow the complex adaptive system to determine how to allocate the resources to meet the emergent needs of the different processes involved in accomplishing its objectives.
When we formulate a dopamine stack, it’s designed to supplement the brain’s building blocks of the precursor nutrients needed for the dopamine-related creative-productive capacities and states.
In addition to these resources, it’s also designed to provide support for the required reactions for the optimal performance of dopaminergic pathways and processes.
It’s essential to boost dopamine to proper levels to reach your full potential. Increased dopamine can be very beneficial to your reward system.
Dopamine plays a prominent role in your physical and mental health. It’s also responsible for your reward system, improved mood, feelings of pleasure, and more. Listening to music and exercise can also increase low dopamine levels in the brain.
Why supply these resources? Why support dopamine signaling pathways and processes?
The big picture answer is that these dopamine pathways and processes play a critical part in boosting motivation, focus, and cognitive flexibility, while also promoting a healthy emotional life, including sensations of reward and pleasure.
Boosting dopamine can be very beneficial for you. The ultimate complexity science answer is a response, which in this case is about the optimization of creative and productive flow states.
Stack of Dopamine Signaling
The following are essential components of the dopamine stack:
Increase the number of compounds used as a precursor.
Give your full support to the path.
Enzymes involved in dopamine synthesis, signaling, and cleanup are supported.
Balanced signaling and neuroprotection are encouraged.
Let’s start putting these puzzle pieces together.
The enzyme tyrosine hydroxylase is the rate-limiting step in the L-DOPA pathway.
This is the enzyme responsible for converting L-tyrosine to L-DOPA.
The legume (bean) Mucuna pruriens is included in this stack because it is a natural source of L-DOPA, which can enter the pathway after this step.
We use this herbal ingredient to provide the same amount of L-DOPA as if a person ate 3-6 ounces of fava beans (fava beans are considered one of the richest food sources of L-DOPA).
As a result, this ingredient promotes dopamine production while avoiding a metabolic bottleneck.
While L-DOPA is further along the pathway than L-tyrosine, dopamine still requires one more enzymatic step. Vitamin B6, in the form of Pyridoxal 5′-phosphate (P5P), is included in the stack to help convert L-DOPA to dopamine.
DOPA decarboxylase (DDC) is the enzyme that converts L-DOPA into dopamine.
Its function is dependent on P5P, a coenzyme form of vitamin B6.
Two amino acid dopamine building blocks are included to provide complete pathway support.
L-tyrosine is a conditionally essential amino acid and the direct precursor to L-DOPA, as previously stated. It is included in this stack as N-Acetyl-L-Tyrosine to supplement the supply of L-tyrosine available for the synthesis of L-DOPA (and then dopamine).
The enzyme phenylalanine hydroxylase produces L-tyrosine from the essential amino acid L-phenylalanine.  We include DL-Phenylalanine in the stack to help maintain healthy L-phenylalanine levels for L-tyrosine synthesis, furthering our goal of complete pathway support.
The stack supports three different steps of the dopamine synthesis pathway, each with its kinetics, by including Mucuna pruriens, N-Acetyl-L-Tyrosine, and DL-Phenylalanine, allowing for a prolonged and sustained availability of precursor resources to be recruited for its synthesis.
The synthesis of all three catecholamine neurotransmitters can be hampered by a lack of any precursor amino acids or cofactors in the catecholaminergic anabolic pathways.
Tetrahydrobiopterin is required as a coenzyme by both tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH).
Tetrahydrobiopterin is produced by an NADPH-dependent pathway from guanosine triphosphate (GTP).
Vitamin B3, in the form of niacinamide, is a precursor to NADPH, and thus indirectly supports the activity of both enzymes in the pathway, which begins with building blocks and ends with dopamine.
Dopamine beta-hydroxylase (DBH) uses vitamin C as a cofactor to convert dopamine to norepinephrine. “Providing building blocks for a pathway and supporting enzyme reactions that build new molecules are all part of designing a neurotransmitter stack.
Supporting the signaling processes involved in listening for and responding to neurotransmitter messages is also a part of it. “
In the dopamine stack, uridine monophosphate plays a unique role.
Although uridine may reduce dopamine receptor density, it appears to improve signal transduction and turnover rate, increasing dopamine-dependent behaviors.
In other words, it may improve the dopamine signaling process’s message-receiving side (listening end) results.
Potassium-evoked dopamine release is also boosted by uridine monophosphate.
Caffeine and theobromine play a role in this stack due to their adenosine receptor antagonism (i.e., slowing of activation).
Because adenosine receptor activation reduces dopaminergic activity, slowing adenosine receptor activity can help to improve dopaminergic signaling indirectly.
Why Should Dopaminergic Pathways and Processes Be Supported?
Dopamine affects a wide range of cognitive and emotional functions. But what if demand for dopamine signaling outstrips supply?
Or if there are any impediments or delays in the production, signaling, or cleanup of dopamine?
It is not the goal to manipulate the dopamine system. Instead, using a complexity science approach, the goal is to provide resources, support regulatory functions, and dopamine levels at multiple points along the interconnected pathways (especially where a metabolic traffic jam is likely), and allow the complex adaptive system to determine how to allocate resources to meet the emergent needs of the various processes involved in the process.
A dopamine stack is created to supplement the brain’s building blocks of the precursor nutrients required for dopamine-related creative-productive capacities and states.
It’s also designed to support the required reactions for the optimal performance of dopaminergic pathways and processes, in addition to these resources.
To reach your full potential, you must increase dopamine levels to proper levels. Increased dopamine levels can help your reward system work better.
Dopamine is important for your physical and mental well-being. It’s also in charge of your reward system, improved moods, pleasurable feelings, and more. Music and exercise can both help to boost low dopamine levels in the brain.
Why Supply These Resources? Why Support Dopamine Signaling Pathways and Processes?
The long answer is that these dopamine pathways and processes are important for boosting motivation, focus, and cognitive flexibility, as well as promoting a healthy emotional life, which includes reward and pleasure sensations.
Increasing dopamine levels can be extremely beneficial to your health.
The ultimate complexity science response is a response, in this case, to optimizing creative and productive flow states.