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Am J Physiol Regul Integr Comp Physiol 288: R1492-R1498, 2005. First published February 24, 2005; doi:10.1152/ajpregu.00554.2004
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Physiological Regulation of Appetite

Reduced feeding response to muscimol and neuropeptide Y in senescent F344 rats

Jessica D. Coppola,1 Barbara A. Horwitz,2 Jock Hamilton,2 James E. Blevins,3 and Roger B. McDonald1

1Department of Nutrition, 2Section of Neurobiology, Physiology, and Behavior, Division of Biological Sciences, University of California, Davis, Davis, California; 3Division of Endocrinology/Metabolism, Veteran's Affairs Puget Sound Health Care System, Seattle, Washington

Submitted 13 August 2004 ; accepted in final form 22 February 2005

Many mammals experience spontaneous declines in their food intake and body weight near the end of life, a stage we refer to as senescence. We have previously demonstrated that senescent rats have blunted food intake responses to intracerebroventricular injections of neuropeptide Y (NPY). In the present study, we tested the hypothesis that responsiveness to GABA, a putative potentiator of NPY's effect, is also diminished. Young and old male F344 rats received injections of NPY, muscimol, (MUS, a GABA-A receptor agonist), combinations of these two agents, and vehicle [artificial cerebrospinal fluid (aCSF)] into the hypothalamic paraventricular nucleus (PVN). Both young and old presenescent rats increased their food intake in response to NPY, MUS, and the combination of the two (in comparison to injections of aCSF). The combination treatment was generally more effective than either NPY or MUS alone. These data are consistent with suggestions that both NPY and GABA play a role in the regulation of feeding behavior. Senescent rats exhibited an attenuated NPY-induced food intake, no increase in response to MUS, and a response to NPY + MUS that was no larger than that of NPY alone. We conclude that PVN injections of GABA, as well as NPY, are less effective in stimulating feeding in senescent rats and suggest that alterations in their signaling pathways play a role in the involuntary feeding decrease seen near the end of life.

anorexia of aging; brain; food intake control; hypothalamus



Address for reprint requests and other correspondence: R. McDonald, Dept. of Nutrition, One Shields Ave., Univ. of California, Davis, CA 95616 (E-mail: rbmcdonald{at}ucdavis.edu)




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W. A. Cupples
Physiological regulation of food intake
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1438 - R1443.
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