title: High-fat diet-induced alterations in the feeding suppression of low-dose nisoxetine, a selective norepinephrine reuptake inhibitor.
abstract: Central noradrenergic pathways are involved in feeding and cardiovascular control, physiological processes altered by obesity. The present studies determined how high-fat feeding and body weight gain alter the sensitivity to the feeding suppression and neural activation to a selective norepinephrine reuptake inhibitor, nisoxetine. Acute administration of nisoxetine (saline: 0, 3, 10, and 30 mg/kg; i.p.) resulted in a dose-dependent reduction in the 24 h refeeding response in male Sprague Dawley rats maintained on standard chow. In a similar fashion, nisoxetine resulted in reductions in blood pressure and a compensatory increase in heart rate. From these studies, the 3 mg/kg dose was subthreshold. In a separate experiment, however, 10 wk exposure to a high-fat diet (60% fat) resulted in weight gain and significant feeding suppression following administration of nisoxetine (3 mg/kg) compared with animals fed a control diet (10% fat). Nisoxetine (3 mg/kg) also resulted in greater neural activation, as measured by c-Fos immunohistochemistry, in the arcuate nucleus of the hypothalamus in animals exposed to the high-fat diet. Such data indicate acute nisoxetine doses that suppress food intake can impact cardiovascular measures. It also suggests that the feeding suppression to a low-dose nisoxetine is enhanced as a result of high-fat diet and weight gain.
authors: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, NJ 08901, USA. ntbello@aesop.rutgers.edu
authors: Nicholas T
authors: NT
authors: Bello
authors: Amy L
authors: AL
authors: Walters
authors: Jessica L
authors: JL
authors: Verpeut
authors: Priscila P
authors: PP
authors: Cunha
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005473:Fluoxetine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D005473:Fluoxetine; C011386:nisoxetine; D009638:Norepinephrine