Anatomic evidence for a neurotoxic effect of (±)-fenfluramine upon serotonergic projections in the rat

Abstract

Immunocytochemistry was used to determine whether (+/-)-fenfluramine causes structural damage to serotonergic (5-HT) neurons. Sections from rat forebrain were examined 4 h, 36 h and 2 weeks after various dose regimens of fenfluramine. At all time points there was a reduction of fine 5-HT axon terminals in the forebrain, while beaded axons were spared. The presence of markedly swollen, fragmented 5-HT axons 36 h after injection is indicative of axonal degeneration, and provides morphologic evidence for a neurotoxic effect of (+/-)-fenfluramine upon 5-HT axon terminals.