A Ketamine Model of Schizophrenia

Schizophrenia is a pervasive mental disorder than greatly reduces the quality of life of the sufferers. Ketamine is an anesthetic and a NMDA receptor antagonist. The “high” from abusing ketamine results in a dissociative state that closely resembles many of the symptoms of schizophrenia. Many researchers are using ketamine to “induce” the behavioral symptoms of schizophrenia in order to better study the disease. Through this research I am attempting to validate whether the ketamine model of schizophrenia also models the neurochemistry of the disorder that is critical for use in the development of new drug interventions. Recently scientists have discovered that levels of certain phospholipids present in the brain are reduced in those with the disease. The animals in this research were dosed with ketamine and brain samples were then obtained at + 20 minutes, 24 h, and 48 h post-injection. An untreated control was also completed. Brains were removed and homogenized in hexane-isopropanol followed by centrifugation at 2500 x g. The hexane-isopropanol was removed under nitrogen and Cs-EDTA and CDCl3-CH3OH were added to the final product. 31P NMR was then performed to determine the levels of phospholipids. The initial results showed similarities to that of the published literature from patients with schizophrenia. However, we were able to improve results with an additional step of sonification that was performed prior to centrifuging. Additionally, the number of cycles of the 31P NMR were increased to improve accuracy and achieve better readings from the data. In summary, the data showed that ketamine produces a change in brain phospholipid levels in a pattern that is consistent with that seen in human schizophrenia