Fenfluramine-induced increases in extracellular hippocampal serotonin are progressively attenuated in vivo during a four-day fenfluramine regimen in rats.
Rats were administered 8 injections of 12.5 mg/kg fenfluramine over a 4-day period. Extracellular hippocampal serotonin levels were monitored in vivo during the 4-day treatment period. Predrug baseline serotonin levels were 0.6 +/- 0.17 pg/5 microliters; 60 min after the first fenfluramine injection extracellular serotonin levels were increased to 28.06 +/- 5.2 pg/5 microliters. Fenfluramine-induced increases in serotonin were substantially reduced on the 2nd through 4th days of the regimen. Baseline serotonin levels were increased on days 2 through 4 of the treatment regimen. In a separate group of animals post-mortem tissue concentrations of serotonin were measured 2 weeks after 1,2,4, or 8 injections of 12.5 mg/kg fenfluramine. There were decreases in serotonin tissue concentrations which were related to the number of fenfluramine injections administered. The in vivo dialysis and post-mortem tissue assay results are consistent with the view that fenfluramine is neurotoxic.
Sabol
K E
KE
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Richards
J B
JB
Seiden
L S
LS
D000818:Animals; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D005277:Fenfluramine / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D005277:Fenfluramine; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine