Sympathetic activation by fenfluramine depletes brown adipose tissue norepinephrine content in rats.
The antiobesity agent fenfluramine (FEN) has been reported to produce an activation of sympathetic neurons to brown adipose tissue (BAT) resulting in thermogenesis. The present study was conducted to determine if FEN-induced activation of BAT is affected by the ambient temperature at which animals are maintained. Body temperature was determined in conscious male Sprague-Dawley rats using implanted temperature transmitters, and sympathetic activation of BAT was determined by measuring norepinephrine (NE) content. Animals maintained at 22 and 4 degrees C incurred a significant decline in core body temperature following FEN administration. FEN produced a significant depletion of BAT NE content, and the magnitude of BAT NE depletion was related to the dose of FEN (-57.4% at 3 mg/kg dose and -75.9% at 10 mg/kg dose). However, the extent of BAT NE depletion was equal at 22 and 4 degrees C. BAT NE depletion by FEN appears to depend on activation of sympathetic neurons because it was prevented by pretreatment with the ganglionic blocker pentolinium (10 mg/kg ip). Furthermore, NE depletion by FEN could be blocked with fluoxetine (10 mg/kg ip) pretreatment, indicating that the action of FEN is mediated through the release of serotonin.
Subramanian
Srividya
S
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, PA 15261, USA.
Vollmer
Regis R
RR
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010425:Pentolinium Tartrate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D005277:Fenfluramine; D005473:Fluoxetine; D018733:Nicotinic Antagonists; D009638:Norepinephrine; D010425:Pentolinium Tartrate; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors