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Neural Integration of Peripheral Signals Implicated in the Control of Energy Homeostasis and Metabolism

Insulin acts at different CNS sites to decrease acute sucrose intake and sucrose self-administration in rats

¹VA Puget Sound Health Care System (151), Seattle, Washington; ²Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle Washington; and ³Faculty of Medicine, University of Latvia, Riga, Latvia

Submitted 1 April 2008 ; accepted in final form 29 May 2008

Findings from our laboratory and others have demonstrated that the hormone insulin has chronic effects within the CNS to regulate energy homeostasis and to decrease brain reward function. In this study, we compared the acute action of insulin to decrease intake of a palatable food in two different behavioral tasks—progressive ratios sucrose self-administration and mu opioid-stimulated sucrose feeding—when administered into several insulin-receptive sites of the CNS. We tested insulin efficacy within the medial hypothalamic arcuate (ARC) and paraventricular (PVN) nuclei, the nucleus accumbens, and the ventral tegmental area. Administration of insulin at a dose that has no chronic effect on body weight (5 mU) into the ARC significantly suppressed sucrose self-administration (75 ± 5% of paired control). However, although the mu opioid DAMGO, [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin acetate salt, stimulated sucrose intake at all four CNS sites, the ventral tegmental area was the only sensitive site for a direct effect of insulin to antagonize acute (60 min) mu opioid-stimulated sucrose feeding: sucrose intake was 53 ± 8% of DAMGO-induced feeding, when insulin was coadministered with DAMGO. These findings demonstrate that free feeding of sucrose, and motivated work for sucrose, can be modulated within unique sites of the CNS reward circuitry. Further, they support the interpretation that adiposity signals, such as insulin, can decrease different aspects of ingestion of a palatable food, such as sucrose, in an anatomically specific manner.

food reward; ventral tegmental area; arcuate nucleus

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