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Balcioglu, A. et al.

Sibutramine, a serotonin uptake inhibitor, increases dopamine concentrations in rat striatal and hypothalamic extracellular fluid.

We measured, using microdialysis, the effects of sibutramine, given intraperitoneally, on brain dopamine and serotonin flux into striatal and hypothalamic dialysates of freely moving rats, and on the uptake of [(3)H]-DA into striatal synaptosomes. For microdialysis experiments, samples collected every 30 min were assayed by high-pressure liquid chromatography, in a single run. Administration of a low dose of sibutramine (2.0 mg/kg, i.p) had no effect on dopamine or serotonin concentrations in striatal dialysates but higher doses increased both: 5 mg/kg increased these concentrations to 196+/-24% (p<0.01) and 221+/-28% (p<0.01) of baseline, respectively; 10 mg/kg increased dopamine to 260+/-66% (p<0.01) and serotonin to 160+/-20% (p<0.05) of baseline. In hypothalamus, the 5 mg/kg sibutramine dose increased the dopamine concentration to 186+/-40% (p<0.05) and that of serotonin to 312+/-86% (p<0.01) of baseline, while the 10 mg/kg (i.p.) dose increased dopamine to 392+/-115% (p<0.01), and serotonin to 329+/-104% (p<0.01) of baseline. In vitro, sibutramine blocked [(3)H]-dopamine uptake into striatal synaptosomes, with an IC(50) value of 3.8 microM. These findings indicate that sibutramine has at least as great an effect on brain extracellular dopamine levels as on brain serotonin, and suggest that the drug's antiobesity action may result from the changes it produces in brain dopamine as well as serotonin metabolism.[1]

References

Sibutramine, a serotonin uptake inhibitor, increases dopamine concentrations in rat striatal and hypothalamic extracellular fluid. Balcioglu, A., Wurtman, R.J. Neuropharmacology (2000) [Pubmed]

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