A 40-year-old chronic alcohol user is admitted with tremors, sweating, and elevated BP. After 24 hours of abstinence, he develops a generalised tonic-clonic seizure. Which GABA-A receptor change underlies this seizure?
- A Upregulation of GABA-A receptors with excessive inhibition
- B Downregulation of GABA-A receptors and upregulation of NMDA receptors during chronic alcohol exposure ✓
- C Complete loss of GABA-A receptors in the cerebellum
- D Selective blockade of GABA-B receptors by acetaldehyde
Correct answer: B. Downregulation of GABA-A receptors and upregulation of NMDA receptors during chronic alcohol exposure
Explanation
Chronic alcohol use potentiates GABA-A (inhibitory) activity, leading to compensatory downregulation of GABA-A receptors and upregulation of NMDA (excitatory) receptors. On sudden abstinence, the loss of GABAergic facilitation combined with excessive NMDA activity creates CNS hyperexcitability, manifesting as withdrawal seizures, tremors, and autonomic instability. This neuroadaptation is the mechanistic basis of alcohol withdrawal syndrome and explains why benzodiazepines (GABA-A agonists) are the treatment of choice.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.