P.1.h.009 Local inactivation of G protein-coupled receptor 88 restores motor and cognitive functions impaired in a rat model of schizophrenia

Abstract

all experiment procedure to demonstrate their effectiveness. The expression of genes coding serotonin receptors (5-HT1, 5-HT2 subtypes), SERT, BDNF and VEGF were measured in prefrontal cortex, midbrain and hippocampus using Quantitative real-time PCR analysis. Moreover, immunohistochemical assay of BDNF and VEGF expression in rat’s hippocampus (CA1) was carried out. Analysis of the expression of genes involved in pathogenesis of depression was performed to show structural validity of model. Diffusion tensor imaging study of the corpus callosum of rats with depression-like behavior were performed with a 7.0 Tesla Bruker BioSpin ClinScan MRI tomograph equipped with a head gradient insert. Results: Action of ultrasonic waves of variable frequency led to a marked reduction of social activity (total time of social contacts, s) in the Social Interaction Test in the experimental group 107±9.8 compared to the control group 216±30.5, (p< 0.001). Fluoxetine and Tianeptine led to restoration of social activity to control levels (228±21.4 and 236±40.6, respectively). Bupropion had no effect on social activity − 142±30.5. In the Porsolt Test, experimental animals showed a significantly higher immobility time (s) (213±15.6) compared to the control group (83±16.3, p< 0.001). Administration of Fluoxetine, Bupropion and Tianeptine reduced the immobility time to control values (129±22.5; 70±16.8; 58±17, respectively). Study of anhedonia development revealed a significant decrease in sucrose preference index in experimental group compared to the control group. RT-qPCR gene expression analysis showed increased expression of SERT gene in all studied structures, decrease expression of 5-HT2A in prefrontal cortex and midbrain, increase 5-HT1A in hippocampus and decrease BDNF in hippocampus of rats after ultrasound. Immunohistochemical assay showed decrease BDNF expression in hippocampus in rats after ultrasound radiation. Diffusion tensor imaging study of the corpus callosum showed decrease numbers of white matter hyperintensities in rats with depression-like behavior, a phenomenon suggested to be linked with white matter pathology. Conclusion: The obtained data allow to conclude that this model meets the main requirements set to animal models of neuropsychiatric disease (face, predictive and construct validity) and can be used in studies of affective disorders and in pre-clinical development of new antidepressants.