Fenfluramine-induced hypothermia is associated with cutaneous dilation in conscious rats.
The antiobesity agent, fenfluramine, produces hypothermia in rodents by an, as yet, uncharacterized mechanism. The present study was conducted in conscious rats to determine if fenfluramine-induced hypothermia was associated with cutaneous dilation. In animals maintained at 16 degrees C, core body temperature (T(CORE)) was measured telemetrically, and tail surface temperature was monitored with thermocouples fixed to the tail (T(TAIL)). D-Fenfluramine (10 mg/kg ip) produced a rapid increase in T(TAIL) of 7.7+/-0.4 degrees C (P<.001) and a decline in T(CORE) of 4+/-0.3 degrees C (P<.001). Two findings indicate that the increase in T(TAIL) was due to the withdrawal of a sympathetic vasoconstrictor tone. First, pretreatment with the ganglionic blocker, pentolinium, prevented fenfluramine-induced changes in T(TAIL). Second, when sympathetic tone to the tail was physiologically withdrawn by increasing the environmental temperature to 28 degrees C, fenfluramine treatment produced no increase in T(TAIL). Moreover, the effects of fenfluramine on T(TAIL) and T(CORE) depended on the uptake of fenfluramine into serotonergic neurons because these effects were markedly attenuated by pretreatment with the selective serotonin re-uptake inhibitor, fluoxetine. The hypothermic effect of fenfluramine occurred despite the fact that total body oxygen consumption increased by 20%. The results suggest that heat loss due to the dilation of the cutaneous circulation contributes to fenfluramine-induced hypothermia.
Subramanian
Srividya
S
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Vollmer
Regis R
RR
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D007035:Hypothermia / Q000139:chemically induced*; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010425:Pentolinium Tartrate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D013623:Tail / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D005277:Fenfluramine; D005473:Fluoxetine; D018733:Nicotinic Antagonists; D010425:Pentolinium Tartrate; D017367:Selective Serotonin Reuptake Inhibitors