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是肥胖流行病的一个促成因素。动物使用与食物刺激相关的线索来确定在哪里获得食物，并确定哪些食物是安全的，最有营养价值和最有价值的。预测食物的线索会激活大脑的奖励系统，刺激寻找食物的行为;重要的是，线索本身就可以刺激饱足动物的食物摄入。因此，已经假设线索诱导的进食导致过量的食物摄入，最终导致肥胖[Castellanos等人，2009; Nijs等人，2010]。食物线索激活中脑边缘多巴胺和阿片样物质系统内的特定核，并且这些区域内的激活与滥用药物产生的激活有显著重叠[Avena et al.，2008; Kelley等人，2000; Rada等人，2005; Spangler等人，2004年]。来自我们实验室和其他实验室的最近发现表明，外侧食欲素神经元偏好与食物和药物奖励相关的线索以及奖励寻求行为，包括线索诱导的对熄灭的食物寻求和药物寻求的恢复[Borgland等人，2009; Cason等人，2010; Cason和Aston-Jones，2013 a; Cason和Aston-Jones，2013 b; Choi等人，2010; Choi等人，2012; Harris等人，2005; Smith等人，2009; Smith和Aston-Jones，2012]。本提案中概述的研究将使用光遗传学和药理学技术的组合来研究特定的食欲素回路，该回路在线索引发的糖精寻求过程中介导对甜食的条件反应。

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.