Fenfluramine: evidence for a neurotoxic action on midbrain and a long-term depletion of serotonin.

A single injection of fenfluramine (100 mumol/kg) produced evidence of neurotoxicity in cresyl violet or silver stained sections of rat brain which was restricted to the serotonergic (B-9) cell group located in the ventromedial midbrain tegmentum. Reacting cells throughout this region exhibited an irregular shape and an intense staining of the cytoplasm, while in the caudal 1/4 of this region the reacting cells also exhibited a perineuronal space. These effects were greatly reduced in the rostral 3/4 of B-9 at 14 and 30 days after fenfluramine. In the caudal 1/4 of B-9 the neurotoxic actions remained prominent and included signs of cellular dissolution. These signs of an irreversible degenerative effect of fenfluramine on cells in the caudal 1/4 of the B-9 region were identical to those seen after p-CA, while the effects in the rostral 3/4 of B-9 were not as prominent. The differential neurotoxic effects of fenfluramine and p-CA on cells in the rostral 3/4 of B-9 were associated with a differential effect on serotonin content of hippocampus and amygdala.