Abstract
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-HT2C/1B receptor agonist, leading to anorexia, whereas food-restricted Ay 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.
Original language | English |
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Pages (from-to) | 1261-1267 |
Number of pages | 7 |
Journal | International Journal of Neuropsychopharmacology |
Volume | 13 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2010 Oct |
Keywords
- 5-HT
- Orexin
- POMC restricted feeding
- satiety
- sibutramine
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health
- Pharmacology (medical)