What does gabapentin do to the brain
Pro Research Analysisby 
Searched over 200M research papers
Gabapentin's Effects on the Brain
Gabapentin and GABA Receptors
Gabapentin, a structural analog of gamma-aminobutyric acid (GABA), has been shown to interact with GABAergic systems in the brain. It increases the expression of δ subunit-containing GABA(_A) receptors, which contribute to tonic inhibitory conductance in neurons, enhancing GABAergic inhibition. This increase in GABAergic activity is thought to underlie some of gabapentin's therapeutic effects, such as its anticonvulsant and anxiolytic properties.
Inhibition of Voltage-Dependent Calcium Channels
Gabapentin inhibits calcium influx through voltage-dependent calcium channels (VD-CCs) by binding to the α2δ subunit of these channels. This inhibition reduces neurotransmitter release, which is crucial for its anticonvulsant and antinociceptive effects . Studies have shown that gabapentin can inhibit up to 70-80% of K(^+)-evoked Ca(^{2+}) influx in certain cell types, indicating a significant impact on calcium channel activity.
Impact on Synaptic Transmission
Gabapentin's inhibition of presynaptic calcium influx leads to a reduction in synaptic transmission. This effect has been observed in both excitatory and inhibitory synapses in the hippocampus and neocortex, where gabapentin reduces the amplitude of evoked postsynaptic currents. This reduction in synaptic activity is consistent with its role in decreasing neuronal excitability and preventing seizures.
Effects on Dopaminergic Neurons
Prenatal exposure to gabapentin has been shown to interfere with the development of ventral midbrain dopaminergic neurons. This interference includes changes in morphology, gene expression, and ATP production, which could have significant implications for brain development and function. These findings suggest that gabapentin can affect neurogenesis and morphogenesis, particularly in developing brains.
Modulation of Neurotransmitter Release
Gabapentin has been found to reduce the release of several monoamine neurotransmitters, including serotonin, which may contribute to its neurobehavioral effects . This reduction in neurotransmitter release is likely linked to its inhibition of calcium channels and subsequent decrease in synaptic transmission.
Increase in Brain GABA Levels
Gabapentin has been shown to increase GABA levels in the brain, as evidenced by magnetic resonance spectroscopy studies in both humans and animals . This increase in GABA concentration is thought to enhance inhibitory neurotransmission, contributing to gabapentin's anticonvulsant and anxiolytic effects.
Conclusion
Gabapentin exerts multiple effects on the brain, primarily through its interaction with GABAergic systems and inhibition of voltage-dependent calcium channels. These actions lead to increased GABA levels, reduced neurotransmitter release, and decreased neuronal excitability, which collectively contribute to its therapeutic effects in conditions such as epilepsy, neuropathic pain, and anxiety. However, caution is advised in its use, particularly during pregnancy, due to its potential impact on brain development.
Sources and full results
Most relevant research papers on this topic