Chronic alcohol use leads to neuroadaptive changes. During withdrawal, the hyperexcitability is primarily due to which of the following?

• A Upregulation of GABA-A receptors
• B Downregulation of NMDA receptors
• C Increased GABA synthesis
• D Decreased GABA-A receptor sensitivity and increased NMDA receptor activity ✓

Explanation

Chronic alcohol enhances GABA-A receptor function and inhibits NMDA glutamate receptors. With abrupt cessation, the downregulated GABA-A receptors become hypofunctional while NMDA receptors are upregulated, leading to unopposed glutamatergic excitation. This causes autonomic hyperactivity, seizures, and delirium tremens. The other options describe changes that would reduce, not increase, excitability.

Reference: Ganong's Review of Medical Physiology, 26th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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