Effects of Fluoxetine Administration on Neuropeptide Y and Orexins in Obese Zucker Rat Hypothalamus

Abstract

GUTIÉ RREZ, ARANTZA, GONZALO SARACÍBAR, LUIS CASIS, ENRIQUE ECHEVARRÍA, VÍCTOR MAN-UEL RODRÍGUEZ, MARIA TERESA MACARULLA, LUIS C. ABECIA, AND MARÍA P. PORTILLO. Effects of fluoxetine administration on neuropeptide Y and orexins in obese Zucker rat hypothalamus. Obes Res. 2002;10: 532-540. Objective: The aim of this work was to study the potential involvement of neuropeptide Y (NPY) and orexins in the anorexigenic mechanism of fluoxetine in obese Zucker rats, assessing the effects of chronic fluoxetine treatment on NPY and orexin immunostaining in several hypothalamic regions. Research Methods and Procedures: Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg intraperitoneally) daily for 2 weeks. The control group was administered 0.9% NaCl solution. Carcass composition was assessed using the official methods of the Association of Official Analytical Chemists. To test the potential thermogenic effect of fluoxetine administration, total body oxygen consumption was measured daily for 60 minutes before fluoxetine or saline injection and for 30 minutes after drug or saline injection. Hypothalamic arcuate and paraventricular nuclei, and the lateral hypothalamic area were immunostained for NPY, orexin A, and orexin B. Commercial kits were used for serum determinations. Results: Chronic fluoxetine administration in obese Zucker rats generated a reduction in body weight gain, food intake, adipocyte size, fat mass, and body protein. A decrease in NPY immunostaining in the paraventricular nucleus, without changes in the arcuate, was observed. However, no changes were observed in the number of neural cells immunostained for orexin A or orexin B in the lateral hypothalamic area. Discussion: Due to the hyperphagic effect of NPY in the paraventricular nucleus, these results suggest that NPY, but not orexins, could be involved in the anorexigenic effect of fluoxetine in obese Zucker rats.

Fluvoxamine Inhibits Weight Gain and Food Intake in Food Restricted Hyperphagic Wistar Rats

“…On the other hand, no significant effect of fluvoxamine was found on NPY immunostaining levels in ARC despite a trend toward a decrease in NPY. These data are supported by evidence reported by Gutierrez et al 15) and Dryden et al 14) for hyperphagic obese Zucker rats. Dryden et al 14) reported conflicting evidence for young Wistar rats: fluoxetine decreased NPY in PVN, increased NPY in ARC, and did not affect DMH.…”

“…16) A decrease of NPY levels in PVN is reportedly induced by fluoxetine. 14,15) These data corresponded with our results, which suggest that fluvoxamine-induced anorexia in our study resulted from reduction of NPY immunostaining in PVN. Those mechanisms might resemble those of fluoxetine.…”

“…Dryden et al 14) reported conflicting evidence for young Wistar rats: fluoxetine decreased NPY in PVN, increased NPY in ARC, and did not affect DMH. These results are inconsistent with the results described by Gutierrez et al, 15) results of our previous study, and those for Dryden's Zucker rats. The changes in regional NPY levels induced by SSRI treatments might result from the appetite level, variation in volume or duration of the agent's administration, or strain differences.…”

“…Those numbers were subtracted from the mean value of each background area, as reported in a previous study. 15) Statistical Analysis Data were analyzed using a twosample Student's t-test. They are presented herein as mean valuesϮS.E.…”

“…Nevertheless, conflicting data related to the appetite control effect of SSRI have been reported; moreover, the weight loss mechanism of SSRI remains unclear. A recent report described appetite controls of SSRI for young rats and obese rats, [14][15][16] but the effect of SSRI on middle-aged rats has not yet been investigated.…”