Hyperthermia-enhanced serotonin (5-HT) depletion resulting from d-fenfluramine exposure is preventable.
Recent findings indicate that elevations in body temperature during acute d-fenfluramine (Fen) exposure enhance long-term 5-HT depletion. Therefore, we hypothesized that when repeated exposure to d-Fen produced repeated elevations in body temperature, 5-HT reductions would be greater in comparison to a single d-Fen exposure. Groups of animals were exposed to d-Fen for 1 or 4 days in a 28 degrees C environment. Exposure to d-Fen in the 28 degrees C environment induced an increase in body temperature and resulted in a long-term decrease in brain 5-HT. However, brain 5-HT was not different between the two groups. An additional experiment revealed that if the initial exposure to d-Fen does not induce elevations in body temperature, then long-term 5-HT depletion can be prevented. We conclude that the central nervous system rapidly adapts to the 5-HT depleting action of d-Fen thereby preventing further decreases in 5-HT concentrations from d-Fen exposure. In addition, this rapid adaptation circumvented the hyperthermia-enhanced 5-HT depletion that results from d-Fen exposure in a warm environment.
Stewart
C W
CW
University of Arkansas for Medical Sciences, Department of Pharmacology and Toxicology, Little Rock 72205, USA.
Slikker
W
W
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D005277:Fenfluramine / Q000494:pharmacology*; D006979:Hyperthermia, Induced; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*
D005277:Fenfluramine; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors