Abstract
The nucleus accumbens in the ventral striatum is considered a pivotal structure in food reward and addictive behavior. Injection of the mu-opioid agonist DAMGO into this structure powerfully stimulates intake of preferred palatable foods such as high fat, but the downstream neural mechanisms are not well understood. We have previously shown that accumbens-hypothalamic projections and orexin-signaling are important since ICV administration of the selective orexin receptor antagonist SB334768 blocks about 70% of the feeding response to accumbens DAMGO. Here we examined the effects of focal injections of the orexin-blocker into brain sites receiving dense orexin-innervation in order to identify the site of action of orexin-signaling. SB334768 injected bilaterally into the ventral tegmental area of rats, significantly attenuated accumbens DAMGO-induced high-fat intake by about 50%. Focal injections into other areas receiving heavy orexin projections, including the arcuate nucleus, paraventricular nucleus of the hypothalamus, and paraventricular nucleus of the thalamus did not significantly change DAMGO-induced high-fat intake. We conclude that orexin-signaling in the ventral tegmental area is crucial for the expression of palatable food consumption elicited by opioid-stimulation of the nucleus accumbens. This pathway is likely to activate the mesolimbic dopamine system eliciting the “wanting” aspect of food reward. Involvement of additional sites of orexin-signaling such as the lateral hypothalamus, locus coeruleus, and or nucleus of the solitary tract in this model for reward-driven appetite remains to be tested. Supported by NIDDK 47348.
Published Version
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