DOPAMINE: FUNCTION, MECHANISM OF ACTION, SYNTHESIS - NEUROPSYCHOLOGY - 2025

The dopamine is a neurotransmitter produced by a wide variety of animals, including both vertebrates and invertebrates beings. It is the most important neurotransmitter in the mammalian central nervous system and participates in the regulation of various functions such as motor behavior, mood and affectivity.

It is generated in the central nervous system, that is, in the brain of animals, and is part of the substances known as catecholamines. Catecholamines are a group of neurotransmitters that are released into the bloodstream and include three main substances: adrenaline, norepinephrine, and dopamine.

Dopamine 3D molecule.

These three substances are synthesized from the amino acid tyrosine and can be produced in the adrenal glands (structures of the kidneys) or in the nerve endings of neurons.

Dopamine is generated in multiple parts of the brain, especially in the substantia nigra, and performs neurotransmission functions in the central nervous system, activating the five types of dopamine receptors: D1, D2, D3, D4 and D5.

In each brain region, dopamine is responsible for carrying out a number of different functions.

The most important are: motor movements, regulation of prolactin secretion, activation of the pleasure system, participation in the regulation of sleep and mood, and activation of cognitive processes.

The dopaminergic system

In the brain there are thousands of dopamine neurons, that is, dopamine chemicals. The fact that this neurotransmitter is so abundant and so distributed among multiple neuronal regions has led to the appearance of dopaminergic systems.

These systems give names to the different dopamine connections in the different areas of the brain, as well as the activities and functions that each of them perform.

In this way, dopamine and its projections can be grouped into 3 main systems.

Ultrashort systems

It makes two groups of main dopaminergic neurons: those of the olfactory bulb and those of the plexiform layers of the retina.

The function of these first two groups of dopamine are mainly responsible for perceptual functions, both visual and olfactory.

Intermediate length system

They include dopamine cells that start in the hypothalamus (an internal region of the brain) and end in the middle nucleus of the pituitary (an endocrine gland that secretes hormones responsible for regulating homeostasis).

This second group of dopamine is mainly characterized by regulating the motor mechanisms and internal processes of the body such as temperature, sleep and balance.

Long systems

This last group includes neurons in the ventral tagmental area (a brain region located in the midbrain), which send projections to three main neuronal regions: the neostriatum (the caudate and putamen nuclei), the limbic cortex, and other limbic structures.

These dopamine cells are in charge of higher mental processes such as cognition, memory, reward or mood.

As we can see, dopamine is a substance that can be found in practically any brain region and that performs an infinite number of mental activities and functions.

For this reason, the correct functioning of dopamine is of vital importance for the well-being of people and there are many alterations that have been related to this substance.

However, before we start to review in detail the actions and implications of this substance, we are going to delve a little more about its operation and its own characteristics.

Synthesis of dopamine

Dopamine is a substance endogenous to the brain and as such, it is produced naturally by the body. The synthesis of this neurotransmitter takes place in the dopaminergic nerve terminals where they are in high concentration of the responsible enzymes.

These enzymes that promote serotonin production are tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (L-DOPA). Thus, the functioning of these two brain enzymes are the main factor that predicts the production of dopamine.

The enzyme L-DOPA requires the presence of the enzyme TH to develop and add to the latter to produce dopamine. Furthermore, the presence of iron is also required for the proper development of the neurotransmitter.

Thus, for dopamine to be generated and distributed normally through different brain regions, the participation of different substances, enzymes and peptides in the body is necessary.

Mechanism of action

The generation of dopamine that we have explained above does not explain the operation of this substance, but simply its appearance.

After the generation of dopamine, dopaminergic neurons begin to appear in the brain, but these must begin to function to carry out their activities.

Like any chemical substance, in order to function dopamine must communicate with each other, that is, it must be transported from one neuron to another. Otherwise, the substance would always remain still and would not carry out any brain activity or carry out the necessary neuronal stimulation.

For dopamine to be transported from one neuron to another, the presence of specific receptors, the dopamine receptors, is necessary.

Receptors are defined as molecules or molecular arrangements that can selectively recognize a ligand and be activated by the ligand itself.

Dopamine receptors are able to distinguish dopamine from other types of neurotransmitters and respond only to it.

When dopamine is released by one neuron, it remains in the intersynaptic space (the space between neurons) until a dopamine receptor picks it up and introduces it to another neuron.

Types of dopamine receptors

There are different types of dopamine receptors, each of them has characteristics and a specific function.

Specifically, 5 main types can be distinguished: D1 receptors, D5 receptors, D2 receptors, D3 receptors and D4 receptors.

D1 receptors are the most abundant within the central nervous system and are found mainly in the olfactory tubercle, in the neostriatum, in the nucleus accumbens, in the amygdala, in the subthalamic nucleus, and in the substantia nigra.

They show a relatively low affinity for dopamine and the activation of these receptors leads to the activation of proteins and the stimulation of various enzymes.

D5 receptors are much rarer than D1 and have a very similar operation.

D2 receptors are present mainly in the hippocampus, in the nucleus accumbens and in the neostriatum, and are coupled to G proteins.

Finally, the D3 and D4 receptors are found mainly in the cerebral cortex and would be involved in cognitive processes such as memory or attention.

Functions of dopamine

Dopamine 2D molecule.

Dopamine is one of the most important chemicals in the brain, and therefore performs multiple functions.

The fact that it is widely distributed throughout the brain regions means that this neurotransmitter is not limited to carrying out a single activity or functions with similar characteristics.

In fact, dopamine participates in multiple brain processes and allows the performance of very diverse and very different activities. The main functions that dopamine carries out are:

Motor movement

Dopaminergic neurons located in the innermost regions of the brain, that is, in the basal ganglia, allow the production of motor movements in people.

D5 receptors seem to be especially involved in this activity and dopamine is a key element in achieving optimal motor function.

The fact that most reveals this role of dopamine is Parkinson's disease, a pathology in which the absence of dopamine in the basal ganglia greatly impairs the individual's ability to move.

Memory, attention and learning

Dopamine is also distributed in the neuronal regions that allow learning and memory, such as the hippocampus and the cerebral cortex.

When not enough dopamine is secreted in these areas, memory problems, inability to maintain attention and learning difficulties can occur.

The feelings of reward

It is probably the main function of this substance since the dopamine secreted in the limbic system allows to experience sensations of pleasure and reward.

In this way, when we perform an activity that is pleasant to us, our brain automatically releases dopamine, which allows us to experience the sensation of pleasure.

Inhibition of prolactin production

Dopamine is responsible for inhibiting the secretion of prolactin, a peptide hormone that stimulates the production of milk in the mammary glands and the synthesis of progesterone in the corpus luteum.

This function is performed mainly in the arcuate nucleus of the hypothalamus and in the anterior pituitary.

Sleep regulation

The functioning of dopamine in the pineal gland allows it to dictate the circadian rhythm in human beings since it allows melatonin to be released and produces the sensation of sleep when you have not sleep for a long time.

Furthermore, dopamine plays an important role in pain processing (low dopamine levels are associated with painful symptoms), and is involved in the self-reflex acts of nausea.

Modulation of mood

Finally, dopamine plays important functions in regulating mood, so low levels of this substance are associated with bad mood and depression.

Pathologies related to dopamine

Dopamine is a substance that carries out multiple brain activities, so its malfunction can lead to many diseases. The most important ones are.

Parkinson's disease

It is the pathology that is most directly related to the functioning of dopamine in the brain regions. In fact, this disease is mainly caused by a degenerative loss of dopaminergic neurotransmitters in the basal ganglia.

The decrease in dopamine translates into the typical motor symptoms of the disease, but it can also cause other manifestations related to the functioning of the neurotransmitter such as memory problems, attention or depression.

The main pharmacological treatment for Parkinson's is based on the use of a dopamine precursor (L-DOPA), which allows to slightly increase the amounts of dopamine in the brain and mitigate the symptoms.

Schizophrenia

The main hypothesis of the etiology of schizophrenia is based on the dopaminergic theory, which states that this disease is due to an overactivity of the dopamine neurotransmitter.

This hypothesis is supported by the efficacy of antipsychotic medications for this disease (which inhibit D2 receptors) and by the ability of drugs that increase dopaminergic activity such as cocaine or amphetamines to generate psychosis.

Epilepsy

Based on various clinical observations, it has been postulated that epilepsy could be a syndrome of dopaminergic hypoactivity, so that a deficit of dopamine production in the mesolimbic areas could lead to this disease.

These data have not been totally counteracted but are supported by the efficacy of drugs that have effective results for the treatment of epilepsy (anticonvulsants), which increase the activity of D2 receptors.

Addiction

In the same mechanism of dopamine that allows the experimentation of pleasure, gratification and motivation, the bases of addiction are also sustained.

Drugs that provide a greater release of dopamine, such as tobacco, cocaine, amphetamines, and morphine, are those that possess the greatest addictive power due to the increase in dopamine produced in the pleasure and reward regions of the brain.

References

1. Arias-Montaño JA. Modulation of dopamine synthesis by presynaptic receptors. Doctoral thesis, Department of Physiology, Biophysics and Neurosciences, CINVESTAV, 1990.
2. Feldman RS, Meyer JS, Quenzer LF. Principles of neuropsychopharmacology. Sunderland, Sinauer, 1997: 277-344.
3. Gobert A, Lejeune F, Rivet JM, Cistarelli L, Millan MJ. Dopamine D3 (auto) receptors inhibit dopamine release in the frontal cortex of freely moving rats in vivo. J Neurochem 1996; 66: 2209-12.
4. Hetey L, Kudrin V, Shemanov A, Rayevsky K, Delssner V. Presynaptic dopamine and serotonin receptors modulating tyrosine hydroxylase activity in synaptosomes of nucleus accumbens of rats. Eur J Pharmacol 1985; 43: 327-30.
5. O'Dowd BF. Structure of dopamine receptors. J Neurochem 1993; 60: 804-16.
6. Poewe W. Should treatment of Parkinson's disease be started with a dopamine agonist? Neurol 1998; 50 (Suppl 6): S19-22.
7. Starr MS. The role of dopamine in epilepsy. Synapse 1996; 22: 159-94.