Hyperthermia-enhanced serotonin (5-HT) depletion resulting from D-fenfluramine (D-Fen) exposure does not evoke a glial-cell response in the central nervous system of rats
Cw. Stewart et W. Slikker, Hyperthermia-enhanced serotonin (5-HT) depletion resulting from D-fenfluramine (D-Fen) exposure does not evoke a glial-cell response in the central nervous system of rats, BRAIN RES, 839(2), 1999, pp. 279-282
D-Fen-induced hyperthermia has been shown to coincide with an enhanced depl
etion of 5-HT and 5-hydroxyindole acetic acid (5-HIAA). Because these obser
vations have relied on D-Fen exposure at multiple environmental temperature
s, some have questioned the validity of the findings. Therefore, this exper
iment was designed to determine if the correlation between elevated body te
mperature and 5-HT depletion could be observed when D-Fen exposure occurred
in one warm environment (28 degrees C) and to determine if a hyperthermia-
enhanced glial-cell response could be evoked by D-Fen exposure. Hyperthermi
a-enhanced 5-HT and 5-HIAA depletion resulting from D-Fen exposure was depe
ndent on body temperature during drug exposure. In the frontal cortex, 5-HT
concentrations ranged from 3 to 45% of control values. Likewise, in the st
riatum and hippocampus, 5-HT concentrations ranged from 13 to 53% and 6 to
40%, respectively. The 5-HIAA concentrations had a wider range than the 5-H
T concentrations for each brain region. In the frontal cortex, striatum and
hippocampus, 5-HIAA ranged from 0 to 93%, 15 to 72% and 0 to 83% of contro
l, respectively. In spite of the substantial reductions in 5-HT, there was
no detectable glial-cell response. D-Fen-induced hyperthermia does not appe
ar to cause generalized damage to neurons in the frontal cortex, striatum a
nd hippocampus. (C) 1999 Published by Elsevier Science B.V. All rights rese
rved.