title: Central dopamine action modulates neuropeptide-controlled appetite via the hypothalamic PI3K/NF-κB-dependent mechanism.
abstract: Hypothalamic neuropeptides, including neuropeptide Y (NPY) and proopiomelanocortin (POMC), have been found to control the appetite-suppressing effect of amphetamine (AMPH). In this study, we have examined whether dopamine receptor (DAR), phosphatidylinositol 3-kinase (PI3K) and nuclear factor-kappaB (NF-κB) are involved in AMPH's action. We administered AMPH to rats once a day for 4 days and assessed and compared changes in hypothalamic NPY, melanocortin receptor 4 (MC4R), PI3K, pAkt and NF-κB expression. We found that the inhibition of DAR increased NPY, but decreased MC4R, PI3K and NF-κB expression, compared with AMPH-treated rats. Moreover, MC4R, PI3K, pAkt and NF-κB increased with the maximum response on Day 2, which was consistent with the response of feeding behavior, but was opposite to the expression of NPY. Furthermore, we found that the intracerebroventricular infusion of the PI3K inhibitor or NF-κB antisense could attenuate AMPH-induced anorexia, and partially reverse the expression of NPY, MC4R, PI3K, Akt and NF-κB back toward a normal level. We, therefore, suggest that DAR-PI3K-NF-κB signaling in the hypothalamus plays functional roles in the modulation of NPY and POMC neurotransmissions and in the control of AMPH-evoked appetite suppression.
authors.affiliation: Institute of Biochemistry and Biotechnology.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Hsieh
authors.forename: P-N
authors.initials: PN
authors.lastname: Chen
authors.forename: C-H
authors.initials: CH
authors.lastname: Yu
authors.forename: D-Y
authors.initials: DY
authors.lastname: Kuo
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000661:Amphetamine; D002867:Chromones; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D009025:Morpholines; D016328:NF-kappa B; D009478:Neuropeptide Y; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011333:Pro-Opiomelanocortin; D051057:Proto-Oncogene Proteins c-akt; D044105:Receptor, Melanocortin, Type 4; D011954:Receptors, Dopamine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Dopamine receptor; NF-κB; NPY; PI3K; POMC; hypothalamus