Effects of repeated dizocilpine treatment on glutamatergic activity in the prefrontal cortex in an animal model of schizophrenia: An in vivo proton magnetic resonance spectroscopy study at 9.4T.

Abstract Repeated exposure to dizocilpine (MK-801) can be used as a model of schizophrenia that incorporates disease progression. Proton magnetic resonance spectroscopy ( 1 H MRS) has been widely used to investigate schizophrenia-related alterations in glutamate (Glu). The purpose of this study was to investigate metabolic alterations in the prefrontal cortex (PFC) in an animal model of schizophrenia by using in vivo 1 H MRS. Because of the spectral overlap of Glu and glutamine (Gln), high-field 1 H MRS with short echo time (TE) was used. A point-resolved spectroscopy sequence was used to measure the levels of Glu and Gln, and the brain metabolites in a volume of interest (22.5 μL) located in the PFC region of rats (n = 13) before and after 6 days of MK-801 (0.5 mg/kg) treatment. Analysis of the spectra showed that the cross-contamination of Glu and Gln can be considered to comparably low. No metabolic parameters were altered ( p  > 0.05). However, differences in Glu and N-acetylaspartate (NAA) levels between two times were significantly correlated ( p 1 H MRS can quantify Glu and Gln with reliably low level of cross-contamination and that repeated exposure to MK-801 induces the progressive development of schizophrenia.