Effects of chronic treatment with dexfenfluramine on serotonin in rat blood, brain and lung tissue.
We have examined the effects of continuous treatment (0.5, 1, 2.5 and 5 mg.kg-1.day-1 for 14 days, using minipumps) with dexfenfluramine (dF) on the concentration of serotonin (5-hydroxytryptamine, 5-HT) in blood, lungs and brain frontal cortex. 5-HT concentration was decreased in whole blood and tissues by the two higher doses (2.5 and 5 mg.kg-1.day-1). The concentration of dF in plasma was above detection limit only in these two treatment groups. The concentration of 5-HT in plasma (extracellular) was not modified dose-dependently, although values higher than controls were noted in the 2.5 mg.kg-1 group. Significant correlations were observed between the concentration of 5-HT in whole blood and that of 5-HT (and 5-HT + 5-HIAA) in frontal cortex. Both correlated inversely with the plasma concentration of dF. These results show that treatment with dF for two weeks reduces the concentration of intracellular 5-HT in peripheral stores (platelets, lung endothelial cells) without a concurrent increase of the extracellular 5-HT pool in blood. Correlation data suggest that whole blood 5-HT content may have a predictive value of dF-induced reductions of 5-HT in brain tissue after long-term treatment.
Celada
P
P
Department of Neurochemistry, CSIC, Barcelona, Spain.
Martín
F
F
Artigas
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F
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005277:Fenfluramine / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood / Q000378:metabolism*
D005277:Fenfluramine; D012701:Serotonin