Neonatal NMDA receptor blockade disrupts prefrontal cortical regulation of social affective behavior: implications for schizophrenia

Neonatal MK-801 exposure in Sprague-Dawley rat pups, especially 0.4 mg/kg, impairs adult social affective behavior, reducing preference for and investigation of distressed conspecifics.

• Why it matters: Developmental NMDAr hypofunction is linked to schizophrenia-related cognitive and emotional deficits, but the mPFC circuit mechanisms for social affective dysfunction are unclear.
• What they did: Rat pups received subcutaneous saline or MK-801 (0.2 or 0.4 mg/kg) neonatally, then adults were tested with Social Affective Preference and Social Interaction; mPFC pyramidal cells and PVINs were modulated chemogenetically.
• The result: mPFC pyramidal inhibition ameliorated MK-801 social deficits, while activation disrupted naive behavior; MK-801 reduced mPFC parvalbumin-positive interneuron density, and PVIN activation alleviated deficits.

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