Hypothalamic orexin and pro-opiomelanocortin activities are essential for the anorexic effects of m-chlorophenylpiperazine in mice.
Hypothalamic pro-opiomelanocortin (POMC) activity is reportedly essential for satiety signalling downstream of serotonin (5-HT). Here we show that food-restricted wild-type mice, which exhibited decreased hypothalamic POMC expression and increased hypothalamic orexin expression, were responsive to m-chlorophenylpiperazine (m-CPP), a 5-HT(2C/1B) receptor agonist, leading to anorexia, whereas food-restricted A(y) mice with decreased hypothalamic POMC and orexin expression, were not. Injection of POMC small interfering RNA (siRNA) oligonucleotide+orexin siRNA oligonucleotide into the third cerebral ventricle was unresponsive to mCPP-induced anorexia, whereas a single injection of POMC or orexin siRNA oligonucleotides elicited a response. The injection of POMC siRNA oligonucleotides suppressed the anorexic effects of sibutramine, a serotonin and noradrenaline re-uptake inhibitor. The injection of orexin siRNA oligonucleotides suppressed the hyperphagia induced by the injection of POMC siRNA oligonucleotides. These findings suggest that functional hypothalamic POMC and orexin activity has a critical role in satiety signalling of mCPP in mice.
Nonogaki
Katsunori
K
Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University Hospital, Aoba-ku, Sendai, Japan. knonogaki-tky@umin.ac.jp
Kaji
Takao
T
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003503:Cyclobutanes / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D006963:Hyperphagia / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D010879:Piperazines / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D012528:Satiety Response / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D001067:Appetite Depressants; D003503:Cyclobutanes; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010879:Piperazines; D034741:RNA, Small Interfering; D017366:Serotonin Receptor Agonists; D011333:Pro-Opiomelanocortin; C015068:1-(3-chlorophenyl)piperazine; C058254:sibutramine