Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB.
Brain research bulletin March 1, 2018 The-Vinh Tran, Se Jin Park, Eun-Joo Shin et al.
Repeated treatment of mice with phencyclidine (PCP), a drug that induces schizophrenia-like symptoms, increased expression of the platelet-activating factor receptor (PAF-R) in the prefrontal cortex and hippocampus, with a greater increase in the prefrontal cortex. This was accompanied by increased activity of the proinflammatory molecule nuclear factor kappa B (NF-κB). Blocking PAF-R with the antagonist ginkgolide B, using PAF-R knockout mice, or inhibiting NF-κB with pyrrolidine dithiocarbamate each reduced PCP-induced abnormal behaviors including reduced sociability, depression, cognitive impairment, and behavioral sensitization. The findings suggest PAF-R drives PCP-induced neuropsychotoxicity through an NF-κB-dependent mechanism and may be linked to schizophrenia-like behavior.