engleski

Rats with altered serotonin homeostasis: an experimental model in neurobiological research

As a part of our research on peripheral and central serotonin we have studied genetic mechanisms underlying the amine homeostasis in rats. After developing a method for "ex vivo" monitoring of platelet serotonin level (PSL) in rats (Life Sci 45(1989)485-92) we have performed breeding selection for the extreme values of this parameter and obtained two sublines of animals with significant differences in PSL (Psych Res 32(1990)167-74); besides platelets, serotonin content in several other tissues was also changed. Further studies demonstrated that changes in kinetics of platelet serotonin transporter (5HTt) underlied the observd differences in PSL. The involved parameter was transporter Vmax and significant differences in 5HTt mRNA and 5HTt protein in platelets (Neurochem Int 33(1999)519-23; Life Sci 69(2001)59-65) of the mentioned sublines were demonstrated. Owing to identical structure of platelet and brain 5HTt we have performed microdyalisis studies in the brains fo selected rats which demonstrated differences in 5HT in hippocampal tissue after specific pharmacological challenge of 5HTt (citalopram) strongly indicating the involvement of central serotonergic mechanisms (Synapse 28(1998)313-21). By recent introduction of the method for "ex vivo" monitoring fo 5HTt kinetics in rats more specific selective breeding of animals for extremes of 5HTt Vmax was started, which gave first succesfull results. In conclusion we have developed sublines of Wistar-derived rats with constitutional difference in the kinetics of 5HTt and consequent differences in general serotonin homeostasis, which could be used as experimental model in neurobiological reesearch.

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