Hyperphagic effects of brainstem ghrelin administration.
The role of ghrelin in feeding control has been addressed from a largely hypothalamic perspective, with little attention directed at ingestive consequences of stimulation of the peptide's receptor, the growth hormone secretagogue receptor (GHS-R), in the caudal brainstem. Here, we demonstrate a hyperphagic response to stimulation of GHS-R in the caudal brainstem. Ghrelin (150 pmol) delivered to the third and fourth ventricles significantly and comparably increased cumulative food intake, with maximal response approximately 3 h after injection. The meal patterning effects underlying this hyperphagia were also similar for the two placements (i.e., significant reduction in the time between injection and first-meal onset, an increase in the number of meals taken shortly after the injection, and a trend toward an increase in the average size of the first meals that approached but did not achieve statistical significance). In a separate experiment, ghrelin microinjected unilaterally into the dorsal vagal complex (DVC) significantly increased food intake measured 1.5 and 3 h after treatment. The response was obtained with a 10-pmol dose, establishing the DVC as a site of action with at least comparable sensitivity to that reported for the arcuate nucleus. Taken together, the results affirm a caudal brainstem site of action and recommend further investigation into multisite interactions underlying the modulation of ingestive behavior by ghrelin.
Faulconbridge
Lucy F
LF
Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. lucyhf@psych.upenn.edu
Cummings
David E
DE
Kaplan
Joel M
JM
Grill
Harvey J
HJ
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D020546:Fourth Ventricle; D054439:Ghrelin; D006963:Hyperphagia / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D036361:Peptide Hormones / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020542:Third Ventricle
D054439:Ghrelin; D036361:Peptide Hormones