DopamineUptakeinSERTKnockoutMiceby.pptVIP

Dopamine Uptake in SERT Knockout Mice by ChronoamperometryX.A. Perez, E. Unger, and A.M. AndrewsDept. of Chemistry, Penn State University, University Park, PA, USA 624.3 Acknowledgements X.A.P is supported by a Penn State Travel Grant. * Introduction * The serotonin (5-HT) neurotransmitter system is thought to play a key role in the regulation of mood, anxiety states and motor activity [1]. * The presynaptic serotonin transporter (SERT) is the primary means by which the concentration of 5-HT in the extracellular space is modulated and it is the molecular target for the largest class of clinically relevant psychiatric drugs (serotonin reuptake inhibitors; SRIs) [2]. * Chronic decreases in 5-HT uptake are believed to eventually result in prolonged increases in extracellular 5-HT. In turn, this fundamental adjustment in serotonergic signaling is thought to lead to adaptive responses, some of which underlie the efficacy of 5-HT reuptake inhibiting drugs [3,4,5] * Recent advancements in molecular biology have yielded a plethora of genetically altered mice including SERT knockout mice. * Autoradiography studies revealed that homozygote knockout mice (SERT-/-) have a complete absence the transporter while heterozygote mice (SERT+/-) have a 50% reduction in transporter density as compared to wildtype mice (SERT+/+) [6]. * Our previous studies using microdyalisis and the method of no-net-flux show a 6-fold and 3-fold increase in the concentration of extracellular 5-HT in striatum of homozygote and heterozygote SERT knockout mice as compared to wildtype mice, respectively. * In addition, our chronoamperometry studies in these mice has shown a 50% decrease in the uptake rate of 5-HT in synaptosomes from heterozygote knockout mice compared to wildtype SERT knockout mice in striatum and frontal cortex. No uptake was observed in synaptosomes from homozygote SERT knockout mice. * Since our long-term goal is to charac