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Wistar-Zagreb 5HT rats: A rodent model with constitutional upregulation/downregulation of serotonin transporter

By selective breeding for the extreme values of platelet serotonin level (PSL) two sublines of rats with constitutional hyperserotonemia/hyposerotonemia were developed. The velocity of platelet serotonin uptake (PSU), the main determinant of PSL, was used as further, more specific, selection criterion and directed breeding for its extremes resulted in two sublines of rats with constitutional up-regulation/down-regulation of platelet 5HT transporter activity, and consequent alterations of entire 5HT homeostasis. These sublines, termed Wistar-Zagreb 5HT rats (WZ-5HT rats), constitute a genetic rodent model described in this chapter. Besides changes in peripheral 5HT homeostasis, high-5HT and low-5HT sublines of physiological conditions, neurochemical differences in the 5HT system between sublines were almost undetectable, but they become clearly evident upon specific pharmacologic challenge, as shown by in vivo microdialysis study. Differential behavioral phenotypes of 5HT sublines in response to various environmental challenges provide further evidence for differences in their brain functioning. Thus, high-5HT rats exhibit enhanced anxiety-like behaviors while depressive-like behavior and higher alcohol intake co-occur in low-5HT animals. Observed functional and behavioural differences between sublines of WZ-5HT rats strongly indicate that the brain serotonergic activity is increased in animals from the high-5HT subline as compared to low-5HT rats. The WZ-5HT rat model may represent an integrative model for serotonin transporter (and serotonin in general) research, incorporating changes at genomic/genetic and phenotypic (neurodevelopmental, structural, biochemical, behavioral etc.) levels and encompassing both central and peripheral 5HT functioning.

Wistar-Zagreb 5HT rat, serotonin, serotonin transporter, platelet, brain, behavior

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