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Journal of Obesity
Volume 2013 (2013), Article ID 457047, 9 pages
http://dx.doi.org/10.1155/2013/457047
Research Article

High-Fat Diet-Induced Alterations in the Feeding Suppression of Low-Dose Nisoxetine, a Selective Norepinephrine Reuptake Inhibitor

1Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, NJ 08901, USA
2Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, NJ 08901, USA

Received 19 October 2012; Accepted 17 December 2012

Academic Editor: Alfredo Halpern

Copyright © 2013 Nicholas T. Bello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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; IP) 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.