Role of Orexin in Conditioned Responding for Saccharin: Implications for Obesity

描述（由申请人提供）：检测和获取食物的能力是一种重要的生存机制；然而，在食物唾手可得且容易获得的现代环境中，这种曾经重要的生存机制现在可能成为肥胖流行的一个促成因素。动物利用与食物刺激相关的线索来确定从哪里获取食物，并确定哪些食物可以安全食用、最有营养价值和最有价值。预测食物的线索会激活大脑奖励系统，刺激寻找食物的行为；重要的是，仅提示就可以刺激饱腹动物的食物摄入。因此，推测提示诱导喂养会导致食物摄入过多，最终导致肥胖[Castellanos et al., 2009; Nijs 等人，2010]。食物线索激活中脑边缘多巴胺和阿片类药物系统内的特定核，并且这些区域内的激活与滥用药物产生的激活有显着的重叠[Avena et al., 2008;凯利等人，2000；拉达等人，2005；斯潘格勒等人，2004]。我们实验室和其他实验室的最新研究结果表明，外侧食欲素神经元偏爱与食物和药物奖励以及寻求奖励行为相关的线索，包括线索诱导的食物寻求和药物寻求的恢复[Borgland et al., 2009;卡森等人，2010；卡森和阿斯顿琼斯，2013a；卡森和阿斯顿琼斯，2013b；崔等人，2010；崔等人，2012；哈里斯等人，2005；史密斯等人，2009；史密斯和阿斯顿琼斯，2012]。该提案中概述的研究将结合光遗传学和药理学技术来研究在线索引发的糖精寻找过程中介导对糖果的条件反应的特定食欲素回路。

DESCRIPTION (provided by applicant): The ability to detect and procure food is an important survival mechanism; however, in the modern environment where food is readily available and easily obtained, this once important survival mechanism may now be a contributing factor to the obesity epidemic. Animals use cues associated with food stimuli to determine where to obtain food, and to identify which foods are safe to eat, most nutritionally valuable and most rewarding. Cues that predict food activate the brain reward system to stimulate food seeking behavior; importantly cues alone can stimulate food intake in sated animals. Therefore cue-induced feeding has been hypothesized to cause excessive food intake culminating in obesity [Castellanos et al., 2009; Nijs et al., 2010]. Food cues activate specific nuclei within the mesolimbic dopamine and opioid systems, and there is a significant overlap in activation within these areas with that produced by drugs of abuse [Avena et al., 2008; Kelley et al., 2000; Rada et al., 2005; Spangler et al., 2004]. Recent findings from our laboratory and others have implicated lateral orexin neurons in preference for cues associated with food and drug reward as well as in reward-seeking behaviors, including cue-induced reinstatement to extinguished food-seeking and drug- seeking [Borgland et al., 2009; Cason et al., 2010; Cason and Aston-Jones, 2013a; Cason and Aston-Jones, 2013b; Choi et al., 2010; Choi et al., 2012; Harris et al., 2005; Smith et al., 2009; Smith and Aston-Jones, 2012]. The studies outlined in this proposal will use a combination of optogenetic and pharmacological techniques to investigate the specific orexin circuitry that mediates conditioned responding to sweets during cue-elicited saccharin-seeking.