Fenfluramine depletes serotonin from the developing cortex and alters thalamocortical organization

Abstract

A previous experiment from our laboratory showed that neonatal destruction of cortical serotoninergic (5-HT) axons with 5,7-dihydroxytryptamine (5,7-DHT) reduced the size of the clusters of vibrissae-related thalamocortical axons. This result suggested an important role for 5-HT in thalamocortical development, but could be questioned because of potentially direct toxic effects of 5,7-DHT on thalamocortical axons. In the present study, 5-HT was depleted from the cortex using a different method, neonatal administration of +fenfluramine, and vibrissae-related patches of thalamocortical afferents were measured when animals reached 6 days of age. Fenfluramine reduced cortical 5-HT levels to 93.9 +/- 6.0% of normal (P < 0.01) and decreased the average area of vibrissae-related lamina IV patches by 23.8 +/- 4.4% (P < 0.05). Depletion of 5-HT with +fenfluramine did not significantly reduce body, brain, or cortical weight, or the overall dimensions of the somatosensory cortex. Thus, these results extend our previous studies by showing that thalamocortical organization can be altered when 5-HT is depleted without the potential for direct toxic effects on thalamic axons.