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|Title:||CHRONIC INHIBITION OF Y5 RECEPTOR ACTIVATION DECREASES FOOD INTAKE IN LACTATING RATS BUT NOT IN CYCLING FEMALE RATS|
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|Authors/Affiliations:||1 Sharon Ladyman*; 1 Nicole Bellefontaine; 1 Barbara Woodside; |
1 Concordia University, Montreal, QC, Canada
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|Content:||Objectives: Neuropeptide Y (NPY) is a potent orexigenic peptide and in the rat its actions are mediated through a family of G-protein coupled receptors (Y1, Y2, Y4 and Y5). While the specific roles of each of the receptor subtypes are yet to be fully elucidated, hypothalamic Y1 and Y5 receptors have both been implicated in the stimulatory effects of NPY on food intake. A number of studies have shown that inactivation of the Y5 receptor, using Y5 antisense oligodeoxynucleotide (ODN) infusion, decreases food intake in male rats, supporting a role for the Y5 receptor in mediating food intake. The aim of the current experiment was to examine the role of the Y5 receptor in the regulation of food intake in cycling female rats and lactating dams, a model of negative energy balance and increased NPY synthesis.|
Methods: Rats were chronically infused with either an antisense ODNs targeted to the NPY Y5 receptor (1.8 nmol/24 hour), an equivalent scrambled ODN or vehicle into the 3rd ventricle for five days. Lactating rats were infused from day 8 postpartum onwards.
Results: Cycling rats treated with Y5 antisense ODN for five days did not show a decrease in food intake. Similarly treated lactating dams, however, did show a significant decreased in food intake compared to the scrambled ODN-treated and vehicle-treated dams. Immunohistochemistry using a Y5 receptor specific antibody was used to confirm that the Y5 antisense ODN treatment was effective at decreasing Y5 protein levels. A significant decrease in the number of Y5 receptor positive cells was detected in the PVN of Y5 antisense ODN treated rats compared to the scrambled ODN or vehicle treated groups.
Conclusions: Because the paraventricular nucleus (PVN) in the hypothalamus is thought to be the major site at which Y5 receptor activation modulates feeding behaviour, it is likely that this change in Y5 receptor protein underlies, at least partially, the decrease in food intake observed in the Y5 antisense ODN treated dams. The lack of significant effect on food intake in the cycling rats suggest that the Y5 receptor may not have a significant role in mediating spontaneous food intake levels in female rats in positive energy balance. During lactation, however, when females are in negative energy balance and NPY levels are high, Y5 receptor activation does apparently contribute to the control of food intake. These results raise the possibility that there are sex differences in the modulation of food intake by Y5 receptor activation in states of positive energy balance and that the contribution of Y5 receptor activation to feeding behaviour is increased in states of negative energy balance.
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