期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 14, 页码 4905-4913出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4404-13.2014
关键词
feeding; mesolimbic; nucleus accumbens; obesity; reward; voltammetry
资金
- National Institutes of Health [R01-DA025634, K01-DA033380]
- National Center for Advancing Translational Sciences Grant [TL1TR000049]
- University of Illinois at Chicago Campus Research Board Pilot Research program
- Chicago Biomedical Consortium
- University of Illinois at Chicago Dean's Scholar Fellowship
Brief, high-concentration (phasic) spikes in nucleus accumbens dopamine critically participate in aspects of food reward. Although physiological state (e. g., hunger, satiety) and associated hormones are known to affect dopamine tone in general, whether they modulate food-evoked, phasic dopamine specifically is unknown. Here, we used fast-scan cyclic voltammetry in awake, behaving rats to record dopamine spikes evoked by delivery of sugar pellets while pharmacologically manipulating central receptors for the gut hunger hormone ghrelin. Lateral ventricular (LV) ghrelin increased, while LV ghrelin receptor antagonism suppressed the magnitude of dopamine spikes evoked by food. Ghrelin was effective when infused directly into the lateral hypothalamus (LH), but not the ventral tegmental area (VTA). LH infusions were made in close proximity to orexin neurons, which are regulated by ghrelin and project to the VTA. Thus, we also investigated and found potentiation of food-evoked dopamine spikes by intra-VTA orexin-A. Importantly, intra-VTA blockade of orexin receptors attenuated food intake induced by LV ghrelin, thus establishing a behaviorally relevant connection between central ghrelin and VTA orexin. Further analysis revealed that food restriction increased the magnitude of dopamine spikes evoked by food independent of any pharmacological manipulations. The results support the regulation of food-evoked dopamine spikes by physiological state with endogenous fluctuations in ghrelin as a key contributor. Our data highlight a novel mechanism by which signals relating physiological state could influence food reinforcement and food-directed behavior.
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