engleski

"Wistar-Zagreb 5HT rat": experimental animal model of constitutionally altered serotonin homeostasis

By selective breeding for the extreme values of platelet serotonin (5HT) level and platelet 5HT uptake, two sublines of Wistar-derived rats ("high-5HT" and "low-5HT" subline) have been developed, demonstrating constitutionally high or low values of both parameters. Molecular genetic studies revealed significant differences in the expression of platelet 5HT transporter (5HTt) at both protein and mRNA levels, between the sublines. Previous neurochemical studies indicated that similar differences might be expected in the expression of neuronal 5HT transporter. In search for possible differences in brain 5HT homeostasis between the mentioned sublines, including compensatory/adaptive changes, molecular genetic, neurochemical and behavioral studies have been performed in brains of the selected animals. Semi-quantitative RT-PCR was used for measuring the expression level of 5HTt, MAO-A and MAO-B in raphe nuclei and prefrontal cortex. A tendency towards higher 5HTt mRNA levels in "high-5HT" subline was observed, while there were no differences in MAO-A or MAO-B mRNA levels between sublines. Levels of 5-HT and its metabolite (5-HIAA) in several brain regions were measured by HPLC. Although 5-HT and 5-HIAA levels themselves were similar between sublines, their ratio, indicating 5HT turnover rate, differed significantly in several brain regions examined, being higher in the "high 5HT"-subline. Two types of behavior mediated by serotonin were investigated: exploratory behavior (nose pokes, rearings) and anxiety (transitions open/close, time spent in open). Animals from "low 5HT"-subline showed significantly higher exploratory behavior and lower level of anxiety than animals from "high 5HT"-subline. These results suggest that our rat sublines have, in addition to periphery, alteration in brain 5HT homeostasis and could serve as useful rodent model for studies of 5HT (dis)regulation.

serotonin; rat; semi-quantitative RT-PCR; HPLC; behavior

nije evidentirano