Phencyclidine and ketamine reproduce both positive and negative symptoms of schizophrenia in healthy volunteers by acting at which molecular target?

• A Presynaptic dopamine D2 autoreceptors
• B Serotonin 5-HT2A receptors
• C Nicotinic acetylcholine receptors
• D NMDA-type glutamate receptors ✓

Explanation

Phencyclidine and ketamine are noncompetitive antagonists at the ion channel of the NMDA glutamate receptor. Their ability to induce a psychosis resembling schizophrenia, including flat affect and withdrawal, underpins the glutamate or NMDA hypofunction hypothesis of schizophrenia. Dopamine antagonism alone explains why current drugs treat positive symptoms poorly against negative symptoms, and serotonergic agonists such as LSD produce perceptual changes without a schizophrenia-like syndrome.

Reference: Stahl's Essential Psychopharmacology, 5th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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