High-fat diet-induced alterations in the feeding suppression of low-dose nisoxetine,a selective norepinephrine reuptake inhibitor

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. © 2013 nicholas t. bello et al.