Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 41, Pages 11075-11082Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3542-07.2007
Keywords
food intake; palatable food; high; fat diet; limbic system; nucleus accumbens; orexin-1 receptor
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Funding
- NIDDK NIH HHS [DK47348, R01 DK047348, DK071082, P30 DK072476, R01 DK071082] Funding Source: Medline
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The overriding of satiety and homeostatic control mechanisms by cognitive, rewarding, and emotional aspects of palatable foods may contribute to the evolving obesity crisis, but little is known about neural pathways and mechanisms responsible for crosstalk between the cognitive and metabolic brain in the control of appetite. Here we show that neural connections between the nucleus accumbens and hypothalamus might be part of this link. Using the well known model of selective stimulation of high-fat intake induced by intra-accumbens injection of the mu-opioid receptor agonist D-Ala2-N-Me-Phe(4)-gly(5)-ol-enkephalin (DAMGO), we demonstrate that orexin signaling in the ventral tegmental area is important for this reward-driven appetite to override metabolic repletion signals in presatiated rats. We further show that accumbens DAMGO in the absence of food selectively increases the proportion of orexin neurons expressing c-Fos in parts of the perifornical hypothalamus and that neural projections originating in DAMGO-responsive sites of the nucleus accumbens make close anatomical contacts with hypothalamic orexin neurons. These findings suggest that direct accumbens-hypothalamic projections can stimulate hypothalamic orexin neurons, which in turn through orexin-1 receptor signaling in the ventral tegmental area and possibly other sites interfaces with the motivational and motor systems to increase intake of palatable food.
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