Abstract
Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, where it is widely distributed. GABA has an important role in neurodevelopment, and depending on the period of development, its action can be excitatory or inhibitory. In prenatal stages, GABA is excitatory, and in the adult stage, GABA acquires an inhibitory function in the nervous system and modulates the function of other organs and systems including the endocrine system and the immune system. Disorders in the function of GABA are responsible for various pathologies, both neurological and non-neurological, and include epilepsy, anxiety, depression, schizophrenia, endocrine disorders and immunological disorders. In the present narrative review, we show that the activity of GABA depends on the synthesis, degradation, membrane transport and the presence of specific GABA receptors, present in both nervous tissue and non-neural tissue. We describe general aspects of the physiology, physiopathology, and pharmacotherapeutics of the GABA system, and finally, we emphasize that although there are multiple GABAergic therapeutic options, more research is required into the GABA system since future applications may be broad.
Highlights
Gamma-aminobutyric acid (GABA) is the most important brain inhibitory neurotransmitter with key roles in the regulation and function of many cortical and subcortical circuits
There are other findings, both in schizophrenic patients and in animal models, related to GABA: reduction in the density of GABAergic neurons, structural alterations of the receptors and disorders in the reuptake of this neurotransmitter. This accumulated evidence suggests the participation of GABA in the genesis of this disease and we have proposed models that propose an interaction of the GABAergic and dopaminergic system in the pathophysiology of schizophrenia [52,53, Benes]
Some studies with benzodiazepines have shown that this GABA agonist agent plays a role in the regulation of the production of corticosteroids by the adrenal cortex and central nervous system in stress situations; extensive studies are required to establish the therapeutic potential of GABAergic agents [77,78]
Summary
Gamma-aminobutyric acid (GABA) is the most important brain inhibitory neurotransmitter with key roles in the regulation and function of many cortical and subcortical circuits. The binding of an agonist to the presynaptic GABA-B receptor decreases the calcium intake, which induces a lower concentration of calcium and a lower release of excitatory neurotransmitters such as glutamate, thereby reducing glutamatergic excitatory activity.
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