engleski

Effect of acute injection of fluoxetine in rats with constitutional upregulation/downregulation of platelet serotonin transporter

Serotonin (5-hydroxytryptamine, 5HT) transporter (5HTT) regulates serotonergic neurotransmission by reuptake of serotonin into the presynaptic neurons. 5HTT represents a target molecule for many antidepressants, such as selective serotonin reuptake inhibitors (SSRI), but they do not provide effective treatment outcome for all individuals. Humans with the low expressing form of the 5HTT gene are often resistant to treatment with SSRI. In search for neurochemical basis of the relationship between 5HTT activity and SSRI efficacy we used Wistar-Zagreb 5HT rats, an animal model with constitutionally high or low platelet serotonin level and uptake (termed high- and low-5HT rats), developed by selective breeding toward extremes of these parameters in our laboratory, as a model for studying various aspects of central and peripheral 5HT function. We examined the acute effect of SSRI, fluoxetine, in Wistar-Zagreb 5HT rats on 5HT-uptake in brain synaptosomes and platelets, as well as platelet and plasma serotonin levels. Fluoxetine (10mg/kg, 60 min postinjection) did not cause changes in the activity of central 5HTT (in cortex, hippocampus and raphe nuclei), in either subline of Wistar-Zagreb 5HT rats. In periphery, the acute administration of fluoxetine (1 and 6mg/kg) resulted in a decrease in platelet 5HTT activity (60 min postinjection) which is differed between the 5HT-sublines. In addition, fluoxetine caused increased plasma serotonin level which was significantly higher in low-5HT animals. If analogous differences in increase of extracellular 5HT level occur in brain, our model may help to understand differential effect of SSRI on therapeutic outcome.

serotonin; fluoxetine; Wistar-Zagreb 5HT rat

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