Abstract The NMDA-R hypofunction model of schizophrenia started with the clinical observation of the precipitation of psychotic symptoms in patients with schizophrenia exposed to PCP or ketamine. Healthy volunteers exposed to acute low doses of ketamine experienced mild psychosis but also negative and cognitive type symptoms reminiscent of the full clinical picture of schizophrenia. In rodents, acute systemic ketamine resulted in a paradoxical increase in extracellular frontal glutamate as well as of dopamine. Similar increase in prefrontal glutamate was documented with acute ketamine in healthy volunteers with 1 H-MRS. Furthermore, sub-chronic low dose PCP lead to reductions in frontal dendritic tree density in rodents. In post-mortem ultrastructural studies in schizophrenia, a broad reduction in dendritic complexity and somal volume of pyramidal cells has been repeatedly described. This most likely accounts for the broad, subtle progressive cortical thinning described with MRI in- vivo. Additionally, prefrontal reductions in the obligatory GluN 1 subunit of the N
📖 افتح في inklap 🔗 DOI 📮 اطلب بحثاً