Effects of fluoxetine administration on neuropeptide y and orexins in obese zucker rat hypothalamus.
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.


METHODS
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.


CONCLUSIONS
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.
Gutiérrez
Arantza
A
Department of Physiology, Faculty of Pharmacy, University of the Basque Country, Paseo de la Universidad 7, 01006 Vitoria, Spain.
Saracíbar
Gonzalo
G
Casis
Luis
L
Echevarría
Enrique
E
Rodríguez
Víctor Manuel
VM
Macarulla
Maria Teresa
MT
Abecia
Luis C
LC
Portillo
María P
MP
D017667:Adipocytes; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D001835:Body Weight; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D048429:Cell Size; D004326:Drinking; D004435:Eating; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000032:analysis / Q000378:metabolism*; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D000068797:Orexins; D009929:Organ Size; D010101:Oxygen Consumption; D051381:Rats; D011924:Rats, Zucker; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002352:Carrier Proteins; D005473:Fluoxetine; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D017367:Selective Serotonin Reuptake Inhibitors; D013963:Thyroid Hormones; D014280:Triglycerides