Poly(I:C) model of schizophrenia in rats induces sex-dependent functional brain changes detected by MRI that are not reversed by aripiprazole treatment

0489601 - ÚPT 2019 RIV US eng J - Journal Article
Dražanová, Eva - Rudá-Kučerová, J. - Krátká, Lucie - Horská, K. - Demlová, R. - Starčuk jr., Zenon - Kašpárek, T.
Poly(I:C) model of schizophrenia in rats induces sex-dependent functional brain changes detected by MRI that are not reversed by aripiprazole treatment.
Brain Research Bulletin. Roč. 137, MAR (2018), s. 146-155. ISSN 0361-9230. E-ISSN 1873-2747
R&D Projects: GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) LO1212; GA MŠMT(CZ) EF16_013/0001775
Institutional support: RVO:68081731
Keywords : aripiprazole * arterial spin labelling * wistar rats * schizophrenia * sex * MRI
OECD category: Pharmacology and pharmacy
Impact factor: 3.103, year: 2018

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 (8 mg/kg on a gestational day 15) in rats taking into account sex-dependent effects and chronic treatment with aripiprazole (30 days), 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.
Permanent Link: http://hdl.handle.net/11104/0283984