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.
D-Fen-induced hyperthermia has been shown to coincide with an enhanced depletion of 5-HT and 5-hydroxyindole acetic acid (5-HIAA). Because these observations have relied on D-Fen exposure at multiple environmental temperatures, some have questioned the validity of the findings. Therefore, this experiment was designed to determine if the correlation between elevated body temperature 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. Hyperthermia-enhanced 5-HT and 5-HIAA depletion resulting from D-Fen exposure was dependent on body temperature during drug exposure. In the frontal cortex, 5-HT concentrations ranged from 3 to 45% of control values. Likewise, in the striatum 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-HT 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 control, respectively. In spite of the substantial reductions in 5-HT, there was no detectable glial-cell response. D-Fen-induced hyperthermia does not appear to cause generalized damage to neurons in the frontal cortex, striatum and hippocampus.
Stewart
C W
CW
University of Arkansas for Medical Sciences, Department of Pharmacology and Toxicology, Little Rock 72205, USA.
Slikker
W
W
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D005277:Fenfluramine / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000737:chemistry / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000172:deficiency / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D005277:Fenfluramine; D005904:Glial Fibrillary Acidic Protein; D006897:Hydroxyindoleacetic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors