Abstract
While animal models for schizophrenia, ranging from pharmacological models to lesions and genetic models, are available, they usually mimic only the positive symptoms of this disorder. Identifying a feasible model of chronic schizophrenia would be valuable for studying the possible underlying mechanism and to investigate emerging treatments. Our hypothesis starts from the observation that combining ketamine with isolation could result in long-lasting neuro-psychological deficits and schizophrenia-like features; thus, it could probably be used as the first model of chronic schizophrenia that emphasizes the characteristic of having a multifactorial etiology. By the means of this study, we investigated the effects of ketamine administration combined with isolation in inducing schizophrenia-like symptoms in male albino rats and the brain reactive oxygen species levels. Our results showed that the number of lines crossings in the open field test, the number of open arm entries in the elevated plus maze, and the spontaneous alternations percentage in the Y-maze were significantly lower in the ketamine + isolation group compared to both the control and ketamine + social housing group (p < 0.05). Furthermore, the ketamine + isolation intervention significantly increased the MDA levels and decreased the GPx levels both in the hippocampus and the cortex of the rats. In addition, our premise of creating a model capable of exhibiting both positive and negative symptoms of schizophrenia was also based on adding the aripiprazole treatment to a group of rats. Therefore, we compared the ketamine + social isolation group with the ketamine + social isolation + aripiprazole group in order to attempt to discover if the antipsychotic drug would significantly decrease the potential positive schizophrenia-like symptoms induced by social isolation and ketamine. Given that we obtained significant results, we cautiously presume that this might be an important step in developing our animal model capable of illustrating both positive and negative symptoms of schizophrenia. This study could be a first step towards the creation of a complex animal model capable of exhibiting the multifactorial origin and manifestation of schizophrenia.
Highlights
Schizophrenia is a multifactorial disease with typically late adolescence or early adulthood onset
We investigated the potential of a combined low dose of ketamine and social isolation in order to establish a better animal model of chronic schizophrenia-like symptoms with the use of male albino rats
In the ketamine plus social isolation group, the number of line crossings in the open field test, the number of open arm entries in the elevated plus maze, and the spontaneous alternations percentage in the Y-maze were significantly lower in the ketamine + isolation group compared to both control and ketamine + social housing group (p < 0.05)
Summary
Schizophrenia is a multifactorial disease with typically late adolescence or early adulthood onset. Positive symptoms can be more understood as the presence of symptoms such as delusions (false fixed beliefs), hallucinations (perceptual disturbances which may occur in any sensory modality but are most commonly auditory), and abnormal psychomotor activity that is usually manifested as grossly disorganized behavior, posturing, and/or catatonia [3]. They are known as psychotic symptoms, whereas negative symptoms are better at describing the absence characterized by social withdrawal, avolition, alogia, and anhedonia. There is a third that is better described as containing the core features of the illness—cognitive symptoms [4]
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