We further found an association between the minor allele in rs211014 (GABRG2) and higher SRE-scores, linked to dizziness and motor incoordination. Genetic variation in GABRG2 has previously been associated with processes involving motor coordination (alcohol withdrawal, febrile- and epileptic seizures).
Alcohol Use Disorder: GABA signalling
the "gamma" in GABA refers to the position of the carbon atom where the amino group is attached, relative to the carboxyl group...To say a carbon is alpha to a carbon would mean that it is right next to it. To say that a carbon is beta to a carbon would mean it is two carbons next to it. To say that a carbon is gamma to a carbon would mean it is three carbons next to it, which the amino-bonded carbon is, relative to the first carbon.
As a stimulant, caffeine blocks calming adenosine receptors and decreases GABAergic transmission, which leads to increased alertness, neurotransmission, and sometimes anxiety... Alcohol increases the effect of GABA (gamma-aminobutyric acid), the brain's main inhibitory neurotransmitter, by acting as an indirect agonist on GABA_A receptors. This enhancement boosts GABAergic neurotransmission, causing decreased neuronal activity, which results in feelings of relaxation and sedation...
Long-term alcohol use can disrupt GABA networks, reducing the body's
ability to produce GABA naturally, often leading to tolerance and
dependence....The cessation of alcohol in dependent individuals causes a significant GABA deficit,
Once in the organism, ethanol metabolism happens in the liver but also in the brain due to the presence of alcohol dehydrogenase (ADH), catalase, and P450 (CYP2E1) in both organs. Such metabolism routes produce mainly three metabolites: acetaldehyde, salsolinol, and acetate (Gil-Mohapel et al., 2019; Wilson and Matschinsky, 2020). After reaching the brain, ethanol and its metabolites induce diverse disturbances such as reduced glucose uptake, increased monocarboxylate uptake, dopaminergic, GABAergic, and glutamatergic alterations (Peana et al., 2017)....Acetaldehyde in the brain causes euphoria at low doses and plays a vital role in ethanol’s reinforcing properties, thereby facilitating alcohol addiction...Acetaldehyde has been shown to stimulate dopaminergic neurons (Melis et al., 2007) and μ opioid receptors (2014)...
"In the absence of alcohol (withdrawal), the GABA activity decreases but the increased glutamate (as compensation) levels remain about the same and leading Glutamate > GABA state."
AI says: Alcohol withdrawal induces severe GABA dysfunction, characterized by reduced inhibitory neurotransmitter levels and decreased
- Reduced Inhibition: Alcohol is a central nervous system depressant that increases GABA activity; in withdrawal, GABA levels drop below normal, leading to CNS hyperactivity.
- Receptor Downregulation: Chronic drinking reduces the sensitivity and number of receptors.
- Hyperglutamatergic State: As GABAergic inhibition declines, glutamate (an excitatory neurotransmitter) activity increases, leading to withdrawal tremors, anxiety, and seizures.
- Impact on Motor System: receptors are highly active in the cerebellum, a region responsible for balance and coordination. Damage to GABA systems can affect motor control and balance (proprioception)
- Stabilization: Neurotransmitter systems generally require 1–5 months to stabilize after stopping alcohol. https://www.reddit.com/r/stopdrinking/comments/rqidln/was_nerd_perusing_articles_interesting_thoughts/
- Back to GABA. Alcohol, like the benzodiazapenes, not only binds to GABA receptors: it desensitizes them. For this reason, the most startling damage to the brain can occur during alcohol withdrawal. What happens is that the brain, having decreased the sensitivity of its GABA receptors over time in response to the constant exposure to alcohol, suddenly displays an excess of activity that can cause damage. This is known as "kindling," and it's one of the reasons that some cases of alcohol withdrawal should be medically managed.