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1 Graduate Groups Psychology and Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: grill{at}psych.upenn.edu.
The central GLP-1 system has been implicated in the control of feeding behavior. Here we explore GLP-1 mediation of the anorexic response to administration of systemic lipopolysaccharide (LPS), and address the relative importance of caudal brainstem and forebrain GLP-1-R for the mediation of the response. Fourth-intracerebroventricular delivery of the GLP-1-R antagonist exendin (9-39) (10 ug) did not itself affect food intake in the 24 h after injection, but significantly attenuated the otherwise robust (~60%) reduction in food intake obtained after LPS (100 ug/kg) treatment. This result highlights a role for caudal brainstem GLP-1-R in the mediation of LPS anorexia, but does not rule out the possibility that forebrain receptors also contribute to the response. Forebrain contribution was addressed by delivery of the GLP-1-R antagonist to the third ventricle with the caudal flow of CSF blocked by occlusion of the cerebral aqueduct. Exendin (9-39) delivery thus limited to forebrain did not attenuate the anorexic response to LPS. These data suggest that LPS anorexia is mediated, in part, by release of the native peptide acting on GLP-1-R within the caudal brainstem.
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