Effects of repeated oral doses of dexnorfenfluramine on 5-HT levels and 5-HT uptake sites in rat brain.
The effects of oral dexnorfenfluramine (DNF; 1-4 mg/kg, twice daily for 4 days), the active metabolite of dexfenfluramine, were examined on rat regional brain indole contents and [3H]citalopram binding. Two hours after the last dose, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were dose-dependently lowered at doses above 1.5 mg/kg, with slight regional differences. Cortical 5-HT uptake sites were reduced only at the highest dose. Above 2 mg/kg DNF also caused a more lasting reduction (4 weeks) of regional indoles and cortical 5-HT uptake sites. At this longer time while the decrease in hippocampal 5-HT levels and cortical 5-HT uptake sites remained essentially constant, cortical and striatal 5-HT levels were lowered less than at 2 h, suggesting a return toward control values.
Gobbi
M
M
Istituto di Ricerche Farmacologiche-Mario Negti, Milano, Italy. gobbi@irfmn.mnegri.it
Bergami
A
A
Caltavuturo
C
C
Valle
F D
FD
Mennini
T
T
Caccia
S
S
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D005277:Fenfluramine / Q000378:metabolism / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D012701:Serotonin / Q000378:metabolism*
D015283:Citalopram; D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid