The regeneration of d,l-fenfluramine-destroyed serotonergic nerve terminals.
The regeneration of serotonergic nerve terminals subsequent to their destruction by high-dose fenfluramine administration was examined. Treating rats with fenfluramine (80 mg/kg over 2 days) destroyed 80% of serotonergic nerve terminals, indicated by reduced maximal [3H]paroxetine binding to 5-hydroxytryptamine (5-HT) uptake sites on synaptic membranes (Bmax) and maximal [14C]5-HT uptake rate into synaptosomes (Vmax). 25 weeks later, these indices of serotonergic nerve terminals had returned to 72% of control. Maximal synaptosomal loading (alpha) with [14C]5-HT also recovered (to 79% of control), reflecting an increased number of serotonergic synaptosomes. This suggests that the rebound in 5-HT uptake site density found after fenfluramine illustrates the regeneration of 5-HT-containing nerve endings.
Westphalen
R I
RI
Clinical Research Centre, Royal Brisbane Hospital Foundation, Bancroft Centre, Herston, Australia.
Dodd
P R
PR
D000818:Animals; D001665:Binding Sites; D005277:Fenfluramine / Q000633:toxicity*; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D005277:Fenfluramine; D012701:Serotonin; D017374:Paroxetine