Fluvoxamine exerts anorexic effect in 5-HT2C receptor mutant mice with heterozygous mutation of beta-endorphin gene.
Serotonin (5-hydroxytryptamine; 5-HT) 2C receptors and the downstream melanocortin pathway are suggested to mediate the anorexic effects of m-chlorophenylpiperazine (mCPP) and fenfluramine. We previously reported that fluvoxamine, a selective serotonin reuptake inhibitor, together with pharmacological inactivation of 5-HT2C receptors exert feeding suppression through activation of 5-HT1B receptors in mice. Here, we report that fluvoxamine exerted anorexic effects in 5-HT2C receptor mutant mice with heterozygous mutation of beta-endorphin gene (2CREnd mice), whereas fluvoxamine had no effect on food intake in age-matched wild-type mice and 5-HT2C receptor mutant mice, which are associated with decreases in hypothalamic proopiomelanocortin (POMC) expression. mCPP suppressed food intake in 5-HT2C receptor mutant mice, 2CREnd mice and age-matched wild-type mice. These results suggest that fluvoxamine-induced feeding suppression requires a perturbation of 5-HT2C receptor and beta-endorphin signalling plus functional hypothalamic POMC activity, whereas mCPP-induced feeding suppression does not always require functional 5-HT2C receptor, beta-endorphin, and POMC activity in mice.
Nonogaki
Katsunori
K
Centre of Excellence, Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. knonogaki-tky@umin.ac.jp
Ohba
Yukie
Y
Wakameda
Mamoru
M
Tamari
Tomohiro
T
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001067:Appetite Depressants; D004435:Eating / Q000187:drug effects*; D016666:Fluvoxamine / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects* / Q000235:genetics*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D001615:beta-Endorphin / Q000235:genetics*
D018687:Antidepressive Agents, Second-Generation; D001067:Appetite Depressants; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D016666:Fluvoxamine; C015068:1-(3-chlorophenyl)piperazine