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GAMMA-AMINOBUTYRIC ACID (GABA)

CHAPTER ONE

INTRODUCTION

1.1 Background of the Study

Gamma-aminobutyric acid (GABA) is a prominent inhibitory neurotransmitter in the central nervous system (CNS), primarily known for its crucial role in regulating neuronal excitability (Miller & Sze, 2021). Discovered in the 1950s, GABA was initially overlooked in favor of other neurotransmitters such as serotonin and dopamine. However, subsequent research has highlighted its significant influence on various physiological and pathological processes, establishing it as a central player in neurophysiology (Nutt, 2021). GABA's primary function is to inhibit synaptic transmission, which helps to maintain the balance between neuronal excitation and inhibition, ensuring proper brain function (Benes et al., 2019).

The synthesis of GABA occurs through the decarboxylation of glutamate, a process catalyzed by the enzyme glutamic acid decarboxylase (GAD) (Kozak et al., 2019). Once synthesized, GABA is stored in vesicles and released into the synaptic cleft upon neuronal activation. Its action is mediated through GABA receptors, which are classified into two major types: GABAA_AA​ and GABAB_BB​ receptors. GABAA_AA​ receptors are ionotropic, mediating fast synaptic inhibition by allowing chloride ions to flow into the neuron, leading to hyperpolarization (Huang et al., 2021). In contrast, GABAB_BB​ receptors are metabotropic, facilitating slower inhibitory signaling through second messenger systems (Kato et al., 2021). This intricate mechanism underscores GABA's pivotal role in maintaining neurotransmission equilibrium and its implications for mental health disorders.

Research has shown that abnormalities in GABAergic signaling are associated with a range of neurological and psychiatric conditions, including anxiety disorders, depression, epilepsy, and schizophrenia (Rao et al., 2019). For instance, decreased GABA levels have been observed in individuals with anxiety disorders, suggesting that GABAergic dysfunction may contribute to heightened anxiety (Duman et al., 2019). Furthermore, GABA has been implicated in the pathophysiology of depression, with studies indicating that

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