Poly(I:C) model of schizophrenia in rats induces sex-dependent functional brain changes detected by MRI that are not reversed by aripiprazole treatment
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29155259
DOI
10.1016/j.brainresbull.2017.11.008
PII: S0361-9230(17)30582-8
Knihovny.cz E-resources
- Keywords
- Aripiprazole *, Arterial Spin Labelling *, MRI *, Schizophrenia *, Sex *, Wistar rats *,
- MeSH
- Antipsychotic Agents pharmacology MeSH
- Aripiprazole pharmacology MeSH
- Magnetic Resonance Imaging MeSH
- Disease Models, Animal MeSH
- Brain diagnostic imaging drug effects physiopathology MeSH
- Cerebrovascular Circulation drug effects physiology MeSH
- Random Allocation MeSH
- Sex Characteristics * MeSH
- Poly I-C MeSH
- Rats, Wistar MeSH
- Schizophrenia diagnostic imaging drug therapy physiopathology MeSH
- Pregnancy MeSH
- Prenatal Exposure Delayed Effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antipsychotic Agents MeSH
- Aripiprazole MeSH
- Poly I-C MeSH
BACKGROUND AND PURPOSE: One of the hallmarks of schizophrenia is altered brain structure, potentially due to antipsychotic treatment, the disorder itself or both. It was proposed that functional changes may precede the structural ones. In order to understand and potentially prevent this unwanted process, brain function assessment should be validated as a diagnostic tool. METHODS: We used Arterial Spin Labelling MRI technique for the evaluation of brain perfusion in several brain regions in a neurodevelopmental poly(I:C) model of schizophrenia (8mg/kg on a gestational day 15) in rats taking into account sex-dependent effects and chronic treatment with aripiprazole (30days), an atypical antipsychotic acting as a partial agonist on dopaminergic receptors. RESULTS: We found the sex of the animal to have a highly significant effect in all regions of interest, with females showing lower blood perfusion than males. However, both males and females treated prenatally with poly(I:C) showed enlargement of the lateral ventricles. Furthermore, we detected increased perfusion in the circle of Willis, hippocampus, and sensorimotor cortex, which was not influenced by chronic atypical antipsychotic aripiprazole treatment in male poly(I:C) rats. CONCLUSION: We hypothesize that perfusion alterations may be caused by the hyperdopaminergic activity in the poly(I:C) model, and the absence of aripiprazole effect on perfusion in brain regions related to schizophrenia may be due to its partial agonistic mechanism.
Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Psychiatry University Hospital and Masaryk University Brno Czech Republic
Institute of Scientific Instruments The Czech Academy of Sciences Brno Czech Republic
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