Journal of Neuroscience Research
December 2014
Jennifer M Timpe, Cheng Z Wang, Jisoo Kim et al.
Phencyclidine (PCP) is a noncompetitive, open channel blocker of the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. When administered to immature animals, it is known to cause apoptotic neurodegeneration in several regions, and this is followed by olanzapine-sensitive, schizophrenia-like behaviors in late adolescence and adulthood. Clarification of its mechanism of action could yield...
Neuropharmacology
February 2010
Yan Xia, Cheng Z Wang, Jie Liu et al.
Phencyclidine is an N-methyl d-aspartate receptor (NMDAR) blocker that has been reported to induce neuronal apoptosis during development and schizophrenia-like behaviors in rats later in life. Brain-derived neurotrophic factor (BDNF) has been shown to prevent neuronal death caused by NMDAR blockade, but the precise mechanism is unknown. This study examined the role of the phosphatidylinositol-3...
Journal of Neurochemistry
May 2009
Gang Lei, Noelle C Anastasio, Yu Fu et al.
Early postnatal blockade of NMDA receptors by phencyclidine (PCP) causes cortical apoptosis in animals. This is associated with the development of schizophrenia-like behaviors in rats later in life. Recent studies show that the mechanism involves a loss of neurotrophic support from the phosphoinositol-3 kinase/Akt pathway, which is normally maintained by synaptic NMDA receptor activation. Here...
Journal of Pharmacology and Experimental Therapeutics
September 2008
Yan Xia, Cheng Z Wang, Jie Liu et al.
Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to be neurotoxic to developing brains and to result in schizophrenia-like behaviors later in development. Prevention of both effects by antischizophrenic drugs suggests the validity of PCP neurodevelopmental toxicity as a heuristic model of schizophrenia. Lithium is used for the treatment of bipolar...
Neuropsychopharmacology
May 2008
Gang Lei, Yan Xia, Kenneth M Johnson
N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) can induce positive and negative symptoms of schizophrenia in humans and related effects in rodents. PCP treatment of developing rats induces apoptotic neurodegeneration and behavioral deficits later in life that mimic some symptoms of schizophrenia. The precise mechanism of PCP-induced neural degeneration is unknown....
Neuropsychopharmacology
May 2007
Cheng Z Wang, Kenneth M Johnson
This study determined the role of caspase-3 in phencyclidine (PCP)-induced neurodegeneration in postnatal rats. PCP administration to postnatal day 7 rats induced a dose-dependent increase in caspase-3 enzymatic activity in frontal cortex, striatum, and hippocampus. Enzymatic activation was present at 4 h, peaked between 6 and 12 h, and disappeared by 24 h. Further, cleaved...
Biochemical Pharmacology
May 1, 2005
Cheng Z Wang, Jared Fridley, Kenneth M Johnson
Phencyclidine (PCP) is an N-methyl-D-aspartate receptor (NMDAR) antagonist known to cause selective neurotoxicity in the cortex following subchronic administration. The purpose of this study was to test the hypothesis that upregulation of the NMDAR plays a role in PCP-induced apoptotic cell death. Corticostriatal slice cultures were used to determine the effects of NMDAR subunit antisense...
International Journal of Developmental Neuroscience
June 5, 2004
Jerrold S. Meyer, Mark Grande, Kenneth M Johnson et al.
50 citations
Abstract 3,4‐Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug‐induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice‐daily MDMA (10 mg/kg s.c.) or saline injections administered from...
Journal of Pharmacology and Experimental Therapeutics
July 1, 2000
Cheng Z Wang, Joel A. Kaufmann, Monica G. Sanchez-Ross et al.
Chronic administration of phencyclidine (PCP) to rats has been demonstrated to produce a sensitized locomotor response to PCP challenge that is associated with apoptotic cell death and an up-regulation of the N-methyl-D-aspartate (NMDA) receptor. To determine the underlying mechanisms, dissociated forebrain cultures were treated for 2 days with 3 microM PCP. After washout of PCP, NMDA was added...