Administration of phencyclidine or ketamine to healthy volunteers produces both positive symptoms such as hallucinations and negative symptoms such as blunted affect and social withdrawal. This observation forms the basis of which hypothesis of schizophrenia?

• A Excess mesolimbic dopamine activity
• B NMDA receptor hypofunction on GABAergic interneurons ✓
• C Serotonin 5-HT2A overactivity
• D Reduced cortical acetylcholine release

Explanation

Phencyclidine and ketamine are noncompetitive antagonists at the NMDA glutamate receptor. Their ability to induce both positive and negative symptoms in healthy subjects supports the glutamate hypothesis, specifically NMDA receptor hypofunction leading to reduced drive on GABAergic interneurons and disinhibition of cortical circuits. Pure dopaminergic agents such as amphetamine produce predominantly positive symptoms, and serotonergic agonists primarily cause perceptual changes without sustained negative symptoms.

Reference: Stahl's Essential Psychopharmacology, 4th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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