LOSS OF SEROTONIN UPTAKE SITES AND IMMUNOREACTIVITY IN RAT CORTEX AFTER DEXFENFLURAMINE OCCUR WITHOUT PARALLEL GLIAL-CELL REACTIONS

The frontal cortices of rats which received either D,L- or D-fenfluram ine (DFEN) for 4 days were examined 18 h to 2 weeks following treatmen t for changes in synaptosomal uptake of serotonin (5HT), paroxetine bi nding, 5HT-immunoreactivity (5HT-IR), and both astrocytic (GFAP) and m icroglial markers. Additional rats received intracerebroventricular in jections of the neurotoxin 5,7-dihydroxytryptamine (DHT). Consistent w ith previous reports, D,L- and DFEN produced dose-dependent losses of both 5HT uptake and paroxetine binding, and loss of 5HT-IR which coinc ided with an abnormal or 'swollen' appearance of immunoreactive axon p rocesses. Recovery of these serotonergic indices was greatest followin g the lowest doses of DFEN, but was absent after 5,7-DHT treatment. No evidence for an increase in GFAP synthesis or microglial activation w as observed in frontal cortices of rats treated with either DFEN or 5, 7-DHT. We conclude that the presence of swollen 5HT-IR axons in the co rtices of both the 5,7-DHT and DFEN groups is insufficient to trigger the glial responses often associated with neuronal degeneration. Thus, it remains to be determined if swollen 5HT-IR axons are a prelude to neurodegeneration, or whether they represent reversible changes in axo nal immunochemistry associated with decreases in 5HT levels. The impli cations of the data for the clinical safety of DFEN are briefly discus sed.