Serotonin and GABA relationship

GABA (gamma-aminobutyric acid) is a neurotransmitter widely distributed in neurons of the cerebral cortex. What does this mean? Well, GABA is a type of substance that is used by neurons of the nervous system when communicating with each other through spaces (called synaptic spaces) by which they connect with each other.

However, GABA is just one of many types of neurotransmitters of the many that act in the brain. That is why it performs some functions that other neurotransmitters do not. Its function is to be an inhibitory neurotransmitter.

But how is it related to serotonin? In this article we will explain what GABA is, what serotonin is, what its functions are and how they interact with each other.

Serotonin and GABA relationship

Serotonin is a neurotransmitter that is commonly spread in the brain which usually raises GABA and thus has inhibitory function, or more accurately, a neuromodulator. Therefore, 5-HTP will increase GABA activity further as a precursor to serotonin.

GABA (gamma-aminobutyric acid) is a neurotransmitter widely distributed in neurons of the cerebral cortex. What does this mean? Well, GABA is a type of substance that is used by neurons of the nervous system when communicating with each other through spaces (called synaptic spaces) by which they connect with each other.

However, GABA is just one of many types of neurotransmitters of the many that act in the brain. That is why it performs some functions that other neurotransmitters do not. Its function is to be an inhibitory neurotransmitter.

GABA, the inhibitory neurotransmitter

GABA is a neurotransmitter (like serotonin or dopamine) and therefore sends chemical messages through the brain and nervous system. In other words, it participates in the communication between neurons.

GABA’s role is to inhibit or reduce neuronal activity, and it plays an important role in behavior, cognition, and the body’s response to stress. Research suggests that GABA helps control fear and anxiety when neurons are over-excited.

On the other hand, low levels of this neurotransmitter are associated with anxiety disorders, sleep problems, depression and schizophrenia. It has also been found that young neurons are more excitable than old ones, and this is due to the role that GABA exerts on the latter.

GABA Contributes to motor control, vision or regulates anxiety, among other cortical functions. There are different drugs that increase GABA levels in the brain and are used to treat epilepsy, Huntington’s disease, or to calm anxiety (for example, benzodiazepines).

It must be borne in mind, however, that little is still known about the functions and processes in which GABA intervenes, and therefore it is hasty to assume that its usefulness is simply that which I have described. In addition, this neurotransmitter intervenes to a greater or lesser extent in other communication dynamics between neurons in which other neurotransmitters play a more relevant role.

GABA’s relationship to fear and anxiety

GABA was discovered in 1950 by Eugene Roberts and J. Awapara, and since then various studies have been carried out to better understand its relationship with anxiety disorders.

In the last decades, research on GABA and benzodiazepines has been numerous, basically to seek treatments against the pathological disorders of fear and anxiety.

These studies have concluded that GABA is involved in these emotions, but it does not seem that its role is other than that of an inhibitory modulator of other neurotransmission systems such as norepinephrine.

In addition, other studies have also provided interesting conclusions regarding how the effect of this neurotransmitter is capable of reducing the effects of stress in individuals.

In an experiment published in the Journal of Neuroscience it was shown that when individuals engage in regular physical exercise, the level of GABA neurons increases in the brain, affecting the ventral hippocampus, a region of the brain linked to the regulation of stress and anxiety.

Another study, this time carried out jointly by Boston University and the University of Utah, found that there is also an increase in this neurotransmitter in yoga practitioners.

How is GABA synthesized?

GABA is synthesized from glutamate decarboxylation thanks to the action of the enzyme glutamate decarboxylase (GAD), a process that occurs in GABAergic neurons in the cerebellum, basal ganglia and many areas of the cerebral cortex, also in the spinal cord.

If the synthesis of this neurotransmitter is inhibited, seizures occur.

GABA receptors

GABA receptors are probably the most numerous in the mammalian nervous system. It is estimated that they are present in at least 30-40% of nerve cells in the human brain.

There are three types of receptors for GABA: GABA-A, GABA-B, and GABA-C. The latter is considered a subtype of the GABA-A receptor, and is also called GABA-A rho.

The GABA-A receptor, the best known

The ionotropic GABA-A receptor, which is located on the plasmatic membrane of the postsynaptic terminal, is the one that is related to benzodiazepines such as Diazepam (better known as Valium), barbiturates or alcohol. It is the best known receptor and is composed of five polypeptide subunits: α, β, γ, δ, ε, each with different functions.

The GABA-B receptor is metabotropic, and it is found in the plasma membrane of the pre- and postsynaptic terminals. The GABA C receptor, like GABA-A, is ionotropic.

Ionotropic and metabotropic receptors

Ionotropic receptors receive this name because they are coupled to an ion channel, which when the ligand binds to them the channel opens and an ion enters or leaves the channel.

In the case of the GABA-A receptor, chlorine (Cl-) enters, which produces the inhibitory response. Its effect is fast because you just have to open the channel to produce the action.

In contrast, metabotropic receptors, such as GABA-B, are slower receptors and are coupled to G proteins, which, specifically in the case of this receptor, lead to the activation of Potassium (K +) channels for the depolarization of the cell.

Relationship with serotonin

Serotonin is a chemical that our neurons produce to communicate with each other. It is a neurotransmitter that also acts as a hormone and that also facilitates key processes for our well-being.

Often, we also define it as the “happiness particle” because of its sedative and antidepressant action, which has a direct relationship with the state of mind.

Just a few months ago, the journal Nature Communications surprised us with an interesting study carried out by University College London.

According to this work, serotonin regulates patience and impulse control. Something essential to promote learning and that persistence necessary to achieve objectives.

The data that is discovered each year about this neurotransmitter is without a doubt fabulous. Thus, among its multiple functions, known for a long time, are for example its ability to regulate our appetite and those sleep cycles, where an excessive level of this compound can lead to insomnia.

In addition, it has an important role in our sexuality, since, when it is at moderately high levels, sexual desire increases. On the contrary, when it is at low levels it can be responsible for the decrease in sexual appetite.

Serotonin also intervenes in anger, aggression, mood regulation, body temperature and the sensation of pain.

The role of the GABAB receptor in the genesis of affective disorders has not yet been fully established. Animal studies suggest that the agonists of these receptors have antidepressant-like activity.

However, this premise can be debated with the study by Nakagawa, who observed in a learned hopelessness model that the long-term increase in GABA neurotransmission was related to hopelessness in rats.

Recent studies have shown that GABAB receptor antagonists show a neuroprotective effect, being capable of producing a rapid increase in brain-derived neurotrophic factor and nerve growth factor.

It has also been found that antidepressants, like GABA receptor antagonists, increase the concentrations of the aforementioned factors, suggesting that both have an effect of attenuation of the neurodegenerative process present in depression.

The depletion of serotonin concentration in the brain blocks the antidepressant effects of GABA antagonists. In addition, serotonin receptors are coupled to the same potassium channels as the GABA receptor; yet another piece of evidence that the GABAergic system plays an important role in modulating mood.

Thanks to advances in brain imaging studies, it has been possible to find the areas with the highest concentrations of the GABA receptor, among which are the molecular layer of the cerebellum, the interpeduncular nucleus, the frontal cortex, the anterior olfactory nucleus and the nucleus of the thalamus.

Furthermore, it has been observed that chronic antidepressant treatment is reflected in a large presence of the GABA receptor.

Serotonin receptors favor the release of GABA

Other indirect evidence of the involvement of the GABAergic system in depression comes from clinical trials demonstrating the antidepressant properties of GABAmimetic compounds.

The study of the role of GABA in the etiopathogenesis of depression regained importance with the emergence of non-invasive brain imaging techniques, such as proton spectroscopy by magnetic resonance imaging, which allows the evaluation of metabolites in the brain.

In a study carried out by Sanacora, 11 subjects with a diagnosis of MDD were analyzed, according to DSM-IV criteria, who were without treatment with psychotropic drugs. A proton magnetic resonance with spectroscopy was performed to determine the GABA values ​​in the occipital cortex.

After this study, SSRIs were administered as monotherapy (fluoxetine or escitalopram) for 5 weeks. GABA concentrations were observed to increase up to 34% in the occipital cortex.

This suggests that SSRIs stimulate the 5HT3 or 5HT2A serotonin receptors, which are found on GABAergic neurons, favoring the release of GABA.

FAQS: Serotonin and gaba relationship

Does GABA affect serotonin?

The inhibitory neurotransmitter GABA (Gamma-AminoButyric Acid) has a stimulating and soothing effect on the brain. Serotonin is also an inhibitory neurotransmitter that allows us to regulate impulses, alleviate discomfort, and is perhaps better known for its function in helping to produce a good attitude.

How is GABA related to depression?

The study showed that, while depression is associated with an increase or decrease in noradrenaline and serotonin concentrations, it is the GABA neurotransmitter that establishes a combined biopsychosocial inhibition pathway that enhances the risk of suicide in people who are biologically and socially insecure.

Does GABA increase dopamine?

The behavior of dopamine neurons is affected greatly by low VTA GABA. … Instead, disinhibition or an improvement in dopamine has been documented following neuronal inhibition of GABA.

What increases GABA in the brain?

Another way that gamma-aminobutyric acid affects brain activity is by altering brain wave patterns. The presence of GABA increases the brain waves associated with a relaxed state (alpha waves) and decreases those associated with stress and anxiety (beta waves).

Can GABA hurt your liver?

Gabapentin, an analogue of gamma-aminobutyric acid (GABA), has seldom been reported to cause liver damage, although the causality is questioned in previous studies.

In this article we explained what GABA is, what serotonin is, what its functions are and how they interact with each other.

If you have any questions or comments please let us know!

References

Bloom, F. 1994. Psychopharmacology. The fourth generation of progress. Raven Press.

Kalueff, A. V., & Nutt, D. J. (2007). Role of GABA in anxiety and depression. Depression and anxiety, 24(7), 495-517.

Petty, F., Trivedi, M. H., Fulton, M., & Rush, A. J. (1995). Benzodiazepines as antidepressants: does GABA play a role in depression?. Biological psychiatry, 38(9), 578-591.