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Ketamine Affects the Expression of ErbB4 in the Hippocampus and Prefrontal Cortex of Rats
Runfang Xie1,2, Shijun Hong2, Yi Ye1
1Department of Analytical Toxicology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Abstract:
Schizophrenia is a severe chronic neuropsychiatric disorder, and its exact pathogenesis remains unclear. This study investigated the effect of ketamine on the expression of ErbB4 (considered a schizophrenia candidate gene) in the hippocampus and prefrontal cortex of rats. Rats were randomly divided into four groups: control, low-dose, medium-dose and high-dose groups. The low-dose, medium-dose and high-dose groups were intraperitoneally injected with 15 mg/kg, 30 mg/kg and 60 mg/kg ketamine, respectively, twice a day (9:00 a.m. and 9:00 p.m.); the control group was administered normal saline. The treatment lasted 7 days. After treatment, rats were euthanized, and their brain tissues were collected and then analyzed by immunohistochemistry. The results of immunohistochemistry staining demonstrated that the ErbB4 protein was expressed exclusively in the CA3 region of the hippocampus and the Cg1 region of the prefrontal cortex. Ketamine administration significantly decreased the expression of ErbB4 in a dose-dependent manner. The high-dose ketamine treatment was found to be optimal for establishing a rat model for schizophrenia. Ketamine induced symptoms similar to schizophrenia in humans. The ketamine-induced rat model for schizophrenia constructed in this study provides novel insights to better understand the pathogenic mechanisms of schizophrenia and aid in drug discovery.
Insights
Ketamine administration significantly reduced ErbB4 protein expression in rat brains, particularly at higher doses. This finding supports ketamine as a tool for modeling schizophrenia, offering insights into disease mechanisms.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- Schizophrenia pathogenesis remains largely unknown.
- ErbB4 is a candidate gene implicated in schizophrenia.
- Ketamine is used to induce psychosis-like symptoms.
Purpose of the Study:
- To investigate ketamine's effect on ErbB4 expression in rat hippocampus and prefrontal cortex.
- To evaluate ketamine's potential in modeling schizophrenia.
Main Methods:
- Rats received varying ketamine doses (15, 30, 60 mg/kg) or saline for 7 days.
- Immunohistochemistry was used to analyze ErbB4 protein expression.
- ErbB4 expression was quantified in specific brain regions (hippocampus CA3, prefrontal cortex Cg1).
Main Results:
- ErbB4 protein was localized to the hippocampus (CA3) and prefrontal cortex (Cg1).
- Ketamine significantly decreased ErbB4 expression in a dose-dependent manner.
- High-dose ketamine (60 mg/kg) was most effective in altering ErbB4 levels.
Conclusions:
- Ketamine administration dose-dependently reduces ErbB4 expression in specific rat brain regions.
- High-dose ketamine effectively models schizophrenia-like symptoms and molecular changes.
- This ketamine-induced rat model offers new avenues for schizophrenia research and drug discovery.
