Molecular validation of the acute phencyclidine rat model for schizophrenia: identification of translational changes in energy metabolism and neurotransmission

Ernst, Agnes, Ma, Dan, Garcia-Perez, Isabel , Tsang, Tsz M., Kluge, Wolfgang, Schwarz, Emanuel, Guest, Paul C., Holmes, Elaine , Sarnyai, Zoltan, and Bahn, Sabine (2012) Molecular validation of the acute phencyclidine rat model for schizophrenia: identification of translational changes in energy metabolism and neurotransmission. Journal of Proteome Research, 11 (7). pp. 3704-3714.

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preclinical model for schizophrenia. Most studies on this model employ methods investigating behavior and brain abnormalities. However, little is known about the corresponding peripheral effects. In this study, we analyzed changes in brain and serum molecular profiles, together with alterations in behavior after acute PCP treatment of rats. Furthermore, abnormalities in peripheral protein expression of first and recent onset antipsychotic free schizophrenia patients were assessed for comparison with the preclinical model. PCP treatment induced hyperlocomotion and stereotypic behavior, which have been related to positive symptoms of schizophrenia. Multiplex immunoassay profiling of serum revealed molecular abnormalities similar to those seen in first and recent onset, antipsychotic free schizophrenia patients. Also, increased insulin levels were detected after administration of a glucose tolerance test (GTT), consistent with previous studies showing changes in insulin signaling in patients with schizophrenia. Finally, schizophrenia-relevant alterations in brain molecules were found in the hippocampus and to a lesser extent in the frontal cortex using liquid-chromatography mass spectrometry and ¹H nuclear magnetic resonance spectroscopy. In conclusion, this study identified behavioral and molecular alterations in the acute PCP rat model, which are also observed in human schizophrenia. We propose that the corresponding changes in serum in both animals and patients may have utility as surrogate markers in this model to facilitate discovery and development of novel drugs for treatment of certain pathological features of schizophrenia.

Item ID: 27242
Item Type: Article (Research - C1)
ISSN: 1535-3907
Keywords: phencyclidine, rat, schizophrenia, multiplexed immunoassay, LC−MS, NMR, GTT
Funders: Stanley Medical Research Institute (SMRI), Innovative Medicines Initiative for Novel Methods leading to New Medications in Depression and Schizophrenia (IMI NEWMEDS), Dutch Fund for Economic Structure Reinforcement (FES)
Projects and Grants: 0908
Date Deposited: 28 May 2013 23:22
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060105 Cell Neurochemistry @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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