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: Nicholas T Bello, Amy L Walters, Jessica L Verpeut, Priscila P Cunha
• Journal: Journal of obesity (J Obes) Vol. 2013 Pg. 457047 ( 2013) ISSN: 2090-0716 [Electronic] United States
• PMID: 23431425 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Proto-Oncogene Proteins c-fos
• Fluoxetine
• nisoxetine
• Norepinephrine

Topics

• Animals
• Appetite Regulation (drug effects, physiology)
• Arcuate Nucleus of Hypothalamus (chemistry)
• Blood Pressure (drug effects)
• Diet, High-Fat (adverse effects)
• Dose-Response Relationship, Drug
• Eating (drug effects)
• Fluoxetine (administration & dosage, analogs & derivatives)
• Heart Rate (drug effects)
• Immunohistochemistry
• Male
• Norepinephrine (antagonists & inhibitors, physiology)
• Proto-Oncogene Proteins c-fos (analysis)
• Rats
• Rats, Sprague-Dawley
• Weight Gain (drug effects)