Brain substances (also called neurotransmitters have an essential role in the functions of the organism.
One of them is dopamine, known for its involvement in reinforcement systems, memory regulation, emotions and movement execution.
This substance is also related to schizophrenia; that is why antipsychotics act on it, blocking its receptors. In this article we will learn about its brain locations, functions, receptors and substances that inhibit or potentiate it.. In addition, we will see how it is related to some disorders such as ADHD or schizophrenia itself.
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Dopamine: characteristics
Dopamine is a very important brain neurotransmitter, which is related to functions such as movement (motor functions), executive functions, emotions, motivation and reinforcement.
This brain substance is highly implicated in psychotic disorders, especially in schizophrenia, since it has been observed that dopamine concentrations are higher than normal in these patients.
In addition, the antipsychotics used to treat these disorders are based primarily on reducing dopamine concentrations.In addition, the antipsychotics used to treat these disorders are mainly based on reducing dopamine levels in the brain (they are dopaminergic antagonists). It has been demonstrated how this reduction of dopamine helps to alleviate the positive symptoms of schizophrenia (delusions, hallucinations…).
Location and functions
Dopamine is found in significant amounts in four pathways or brain systemsThe nigrostriatal pathway (substantia nigra and basal ganglia), the mesolimbic pathway, the mesocortical pathway and the tuberoinfundibular pathway.
Let’s see which functions are related to these four pathways or systems:
1. nigrostriatal system
Within this system (located in the midbrain), dopamine is mainly found in the areas of the basal ganglia and the substantia nigra.. In the nigrostriatal system, dopamine has a movement-related function.
On the other hand, it has been observed that in patients with Parkinson’s disease, dopamine is deficient in this area. This makes sense, since in Parkinson’s disease movement is especially affected (it is its most characteristic symptom).
2. Mesolimbic system
The second location of dopamine is the mesolimbic system, which is located, as above, in the midbrain.which is located, like the previous one, in the midbrain. Specifically, in the limbic system and the nucleus accumbens (areas involved in reinforcement and emotions). Thus, in the mesolimbic system, dopamine is especially related to emotions and positive reinforcement; these are areas that are activated when we experience pleasure or pleasant sensations.
This system is implicated in the positive symptoms of schizophrenia (the high concentration of dopamine in the mesolimbic has been related to these symptoms). Recall that positive symptoms include “excess” symptoms, such as hallucinations, disorganized or extravagant behavior, delusions, etc.
3. Mesocortical system
Dopamine is also found in the mesocortical system, located in the prefrontal midbrain.. It is for this reason (its prefrontal location) that the presence of dopamine in this system is related to executive functions: planning, attention, cognition….
Contrary to the previous one, the mesocortical system is related to the negative symptoms of schizophrenia (abulia, affective flattening, anhedonia, apathy…); that is to say, the “default” symptoms.
4. Tuberoinfundibular system
The fourth system where we find dopamine, is located in the hypothalamus and the pituitary gland (these structures are connected through the infundibulum). Dopamine in the tuberoinfundibular system inhibits prolactin, a hormone related to the secretion of breast milk during pregnancy. That is, dopamine here exerts hormonal control.
When taking antipsychotics (which decrease the concentration of dopamine in the four aforementioned pathways), prolactin increases in this particular system, producing side effects such as galactorrhea (secretion of milk in people who are not breastfeeding) and increased mammary size.
Receptors
Receptors are structures found in the membrane of cells that allow the connection of neurotransmitters, i.e. they allow the transmission of neurotransmitters.i.e. they allow the transmission of information, and the increase of certain brain substances.
Generally, drugs (e.g. antipsychotics, antidepressants…) act on cell receptors, increasing or inhibiting the secretion of certain substances (depending on whether their mechanism of action is agonist [increase] or antagonist [decrease or inhibition]).
Each type of neurotransmitter has specific receptors; in the case of dopamine, there are two types: presynaptic and postsynaptic. As dopamine receptors we find the D1 and D5 receptors (postsynaptic), and the D2, D3 and D4 receptors (pre or postsynaptic).
The receptors altered in schizophrenia are the D2 receptors; they are involved in reinforcement and addictions. In schizophrenia, there is a hyperactivation of these receptors, and an increase of the dopaminergic substance (dopamine). Antipsychotics, as mentioned above, reduce the concentration of this substance.
Agonists
Agonist substances or drugs increase the concentration of “X” substance in the brain.. In other words, agonists can be said to increase the effect of that substance. Each brain neurotransmitter (such as noradrenaline, serotonin…) has its own agonist substances. These substances can be natural substances, drugs, pharmaceuticals, etc….
In the case of dopamine, we find four main agonist substances (stimulant substances):
1. apomorphine
Apomorphine, curiously, is a dopamine agonist substance, but at high doses; at low doses, however, it acts as an antagonist (inhibiting its effect). It is a synthetic derivative of another substance, morphine. Apomorphine is used for the treatment of Parkinson’s disease.
2. Amphetamines
Amphetamines are drugs that act on dopamine (DA) and noradrenaline (NA). They are potent CNS (Central Nervous System) stimulants, and their mechanism of action is based on reversing the reuptake pumps of these substances; that is, they increase the release of these substances and inhibit their reuptake.
3. Cocaine
Another dopamine agonist substance is cocaine, another well-known drug, which is extracted from coca leaves (a type of bush), and which can also be synthesized in the laboratory. Cocaine acts by inhibiting the reuptake of dopamine, causing its levels to increase.
4. Methylphenidate
Finally, methylphenidate, a drug known to be indicated and used in cases of ADHD (Attention Deficit Hyperactivity Disorder), also inhibits dopamine reuptake, increasing its concentration in the brain.
Paradoxically, although methylphenidate is a stimulant, it is a drug that has been shown to improve attention and reduce hyperactivity (and impulsivity) in children with ADHD. In children with ADHD, deficient levels of dopamine have been found in the prefrontal area of the frontal lobe (as it is very rapidly reuptaken).
Antagonists
On the other hand, antagonist substances inhibit the action of “X” substance, decrease its concentration or reduce its effect.. The main dopamine antagonists are the antipsychotic drugs, which can be classical or typical (first generation) or atypical (second generation).
What antipsychotics do, as we have already mentioned, is to block the D2 receptors of dopamine, to reduce or inhibit the effect of this substance; that is, they act as dopamine antagonists.
Antipsychotics are used especially in psychotic disorders, although they also have indications for cases of OCD (Obsessive Compulsive Disorder), chronic pain, movement disorders and tics, agitation, confusion, delirium, alcohol deprivation…. Indications will always depend on the type of antipsychotic and its properties.