The Feeding Response to Melanin-Concentrating Hormone Is Attenuated by Antagonism of the NPY Y1-Receptor in the Rat

Dec 26, 2001Endocrinology

Blocking a specific brain receptor reduces melanin-concentrating hormone's effect on feeding in rats

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Abstract

MCH and NPY stimulated food intake in male Sprague Dawley rats, with intake recorded at 5.9 g and 3.6 g, respectively.

MCH and NPY are orexigenic peptides found in specific brain regions related to feeding.
Administration of MCH or NPY significantly increased food intake compared to a control vehicle.
Two different antagonists of the Y(1)-receptor substantially reduced MCH-induced feeding by 73% and 86%.
Coadministration of NPY and MCH did not enhance food intake beyond the levels induced by NPY alone.
The inhibition of MCH-induced feeding by the antagonists indicates that MCH's appetite-stimulating effects are linked to the Y(1)-receptor.

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Melanin-concentrating hormone (MCH) and NPY are orexigenic peptides localized in the lateral hypothalamic area and arcuate nucleus, respectively. Although both NPY- and MCH-containing fibers innervate areas of the hypothalamus implicated in feeding, the extent to which the regulation of appetite is dependent on interactions between these peptides is unknown. Daytime feeding responses to 2 nmol MCH, 1 nmol NPY, or vehicle were investigated in male Sprague Dawley rats previously implanted with intracerebroventricular cannulas. The effects of prior administration of the Y(1)-receptor antagonists BIBO 3304 (20 nmol) or GR231118 (5 nmol) on these responses were examined. NPY and MCH stimulated food intake relative to vehicle (4 h intake, 5.9 +/- 0.7 and 3.6 +/- 0.2 g, respectively; P < 0.0001). BIBO 3304 and GR231118 significantly inhibited MCH- induced feeding by 73% (P < 0.01) and 86% (P < 0.01), respectively, at 2 h. Coadministration of NPY and MCH did not increase food intake above that in response to NPY alone; however, prior administration of BIBO 3304 resulted in a less marked inhibition of feeding (P < 0.05, 30 min only). Inhibition of MCH-induced feeding by two structurally different NPY Y(1)-receptor antagonists provides strong evidence that the orexigenic action of MCH involves the Y(1)-receptor.

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The Feeding Response to Melanin-Concentrating Hormone Is Attenuated by Antagonism of the NPY Y1-Receptor in the Rat

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