Fluvoxamine, a selective serotonin reuptake inhibitor, and 5-HT2C receptor inactivation induce appetite-suppressing effects in mice via 5-HT1B receptors.
Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream melanocortin pathway are suggested to mediate the appetite-suppressing effects of 5-HT drugs such as m-chlorophenylpiperazine (mCPP) and fenfluramine. Here, we report that fluvoxamine (3-30 mg/kg), a selective serotonin reuptake inhibitor (SSRI), in the presence of SB 242084 (1-2 mg/kg), a selective 5-HT2C receptor antagonist, exerts appetite-suppressing effects while fluvoxamine or SB 242084 alone has no effect. The appetite-suppressing effects were attenuated in the presence of SB 224289 (5 mg/kg), a selective 5-HT1B receptor antagonist. Moreover, CP 94253 (5-10 mg/kg), a selective 5-HT1B receptor agonist, exerted appetite-suppressing effects and significantly increased hypothalamic pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) gene expression and decreased hypothalamic orexin gene expression. These results suggest that fluvoxamine and inactivation of 5-HT2C receptors exert feeding suppression through activation of 5-HT1B receptors, and that 5-HT1B receptors up-regulate hypothalamic POMC and CART gene expression and down-regulate hypothalamic orexin gene expression in mice.
Nonogaki
Katsunori
K
Center of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Japan. knonogaki-tky@umin.ac.jp
Nozue
Kana
K
Takahashi
Yukiko
Y
Yamashita
Nobuyuki
N
Hiraoka
Shuichi
S
Kumano
Hiroaki
H
Kuboki
Tomifusa
T
Oka
Yohsitomo
Y
D000704:Analysis of Variance; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects; D016666:Fluvoxamine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D000068797:Orexins; D010879:Piperazines / Q000494:pharmacology; D010881:Piperidones / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D013997:Time Factors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D001067:Appetite Depressants; D016666:Fluvoxamine; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000068797:Orexins; D010879:Piperazines; D010881:Piperidones; D011333:Pro-Opiomelanocortin; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013141:Spiro Compounds; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C108518:SB 22489G; C015068:1-(3-chlorophenyl)piperazine