A 38-year-old chronic alcohol user is admitted with a generalised tonic-clonic seizure on day 2 of abstinence. He develops tremors, diaphoresis, tachycardia, and hypertension. The mechanism of alcohol withdrawal seizures is best explained by:

• A Rebound upregulation of GABA-A receptors leading to generalised CNS inhibition
• B Excess dopamine release in mesolimbic pathways
• C Glutamate (NMDA receptor) upregulation and GABA downregulation causing CNS hyperexcitability ✓
• D Serotonin syndrome secondary to alcohol-induced 5-HT release

Explanation

Chronic alcohol use leads to adaptive changes: downregulation (desensitisation) of GABA-A receptors and upregulation (sensitisation) of NMDA glutamate receptors. Upon abrupt cessation, the unopposed NMDA excitation combined with reduced GABAergic inhibition produces CNS hyperexcitability manifesting as tremors, autonomic instability, and seizures. This neurochemical imbalance is the rationale for treating withdrawal with benzodiazepines (GABA-A enhancers). Dopamine excess is implicated in alcohol craving and reward, not withdrawal seizures.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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Written and medically reviewed by the StethoPrep medical team.