期刊
NEUROSCIENCE
卷 180, 期 -, 页码 129-137出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2011.02.016
关键词
ghrelin; GHS-R1A; food motivation; operant conditioning; ventral tegmental area; nucleus accumbens
资金
- EU [FP7-HEALTH- 2009-241592, FP7-KBBE-2009-3-245009, FP7-KBBE-2010-4-266408]
- Swedish Medical Research Council [K2007-54X-20328-013]
- ALF Goteborg [138741]
- Swedish Foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research [A305-188]
- Swedish Institute
Ghrelin, a circulating orexigenic stomach-derived hormone, has recently been implicated in extra-homeostatic feeding, increasing food reward and food-motivated behavior. The precise target site(s) for ghrelin's effects on food reward have yet to be elucidated. The neurocircuitry underpinning food-motivated behavior involves, in particular, the dopamine cells of the ventral tegmental area (VTA) that project to the nucleus accumbens (NAcc). Ghrelin stimulation in both of these mesolimbic reward areas increases chow intake. Here we sought to determine if ghrelin acts directly within these mesolimbic reward areas to increase food reward/motivation in studies that combine feeding behavior, pharmacology, and neuroanatomy. We found that motivated behavior for a sucrose reward, assessed in an operant conditioning paradigm in rats, was increased when ghrelin was microinjected directly into the VTA but not into the NAcc. By contrast, ghrelin administration to both areas increased the free feeding of chow. Importantly, in a state of overnight food restriction, where endogenous levels of ghrelin are increased, ghrelin receptor (GHS-R1A) blockade in the VTA was sufficient to decrease the motivation to work for a sugar reward. Blockade of the GHS-R1A in VTA or NAcc was not sufficient to reduce fasting-induced chow hyperphagia. Taken together our data identify the VTA but not the NAcc as a direct, necessary, and sufficient target site for ghrelin's action on food motivation. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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