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1 Department of Nutrition, University of California, Davis, CA, USA
2 Section of Neurobiology, Physiology, and Behavior, Division of Biological Sciences, University of California, Davis, CA, USA
3 Division of Endocrinology/Metabolism, VA Puget Sound Health Care System, Seattle, WA, USA
* To whom correspondence should be addressed. E-mail: rbmcdonald{at}ucdavis.edu.
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 (ICV) injections of neuropeptide Y (NPY). In the present study, we tested the hypothesis that responsiveness to gamma amino butyric acid (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.
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