Hypothalamic orexin and pro-opiomelanocortin activities are essential for the anorexic effects of m-chlorophenylpiperazine in mice

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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. © 2010 CINP.

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Nonogaki, K., & Kaji, T. (2010). Hypothalamic orexin and pro-opiomelanocortin activities are essential for the anorexic effects of m-chlorophenylpiperazine in mice. International Journal of Neuropsychopharmacology, 13(9), 1261–1267. https://doi.org/10.1017/S1461145710000672

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