There is emerging evidence implicating glucagon-like peptide-1 (GLP-1) in reward, including palatable food reinforcement and alcohol-based reward circuitry. While recent findings suggest that mesolimbic structures, su...There is emerging evidence implicating glucagon-like peptide-1 (GLP-1) in reward, including palatable food reinforcement and alcohol-based reward circuitry. While recent findings suggest that mesolimbic structures, such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc), are critical anatomical sites mediating the role of GLP-1’s inhibitory actions, the present study focused on the potential novel impact of GLP-1 within the habenula, a region of the forebrain expressing GLP-1 receptors. Given that the habenula has also been implicated in the neural control of reward and reinforcement, we hypothesized that this brain region, like the VTA and NAc, might mediate the anhedonic effects of GLP-1. Rats were stereotaxically implanted with guide cannula targeting the habenula and trained on a progressive ratio 3 (PR3) schedule of reinforcement. Separate rats were trained on an alcohol two-bottle choice paradigm with intermittent access. The GLP-1 agonist exendin-4 (Ex-4) was administered directly into the habenula to determine the effects on operant responding for palatable food as well as alcohol intake. Our results indicated that Ex-4 reliably suppressed PR3 responding and that this effect was dose-dependent. A similar suppressive effect on alcohol consumption was observed. These findings provide initial and compelling evidence that the habenula may mediate the inhibitory action of GLP-1 on reward, including operant and drug reward. Our findings further suggest that GLP-1 receptor mechanisms outside of the midbrain and ventral striatum are critically involved in brain reward neurotransmission.展开更多
肥胖的形成和发展受生物、心理和社会因素的共同作用,其中食物奖赏对肥胖的产生有重要的作用。食物是一种自然奖赏,它指机体天生对食物的渴望和依赖。食物奖赏包括"wanting"、"liking"以及"learning&reinf...肥胖的形成和发展受生物、心理和社会因素的共同作用,其中食物奖赏对肥胖的产生有重要的作用。食物是一种自然奖赏,它指机体天生对食物的渴望和依赖。食物奖赏包括"wanting"、"liking"以及"learning&reinforcement"三个成分,每个成分由相应的神经通路表征。食物奖赏调控机体的摄食行为并以此调控体重变化。目前,关于肥胖与食物奖赏关系的理论模型主要有刺激—敏感化理论、奖赏过度理论以及奖赏不足理论。采用横断面设计、前瞻研究设计和纵向被试内重复测量设计,使用食物图片线索和直接给予美味奶昔的技术方法,人类脑成像研究从不同侧面为以上三个理论模型提供了证据。除此之外,食物奖赏还受基因的调控。目前,研究者关注较多的是多巴胺D2受体基因Taq IA rs1800497的多态性和FTO基因rs9939609的多态性对食物奖赏及体重改变的调控。展开更多
文摘There is emerging evidence implicating glucagon-like peptide-1 (GLP-1) in reward, including palatable food reinforcement and alcohol-based reward circuitry. While recent findings suggest that mesolimbic structures, such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc), are critical anatomical sites mediating the role of GLP-1’s inhibitory actions, the present study focused on the potential novel impact of GLP-1 within the habenula, a region of the forebrain expressing GLP-1 receptors. Given that the habenula has also been implicated in the neural control of reward and reinforcement, we hypothesized that this brain region, like the VTA and NAc, might mediate the anhedonic effects of GLP-1. Rats were stereotaxically implanted with guide cannula targeting the habenula and trained on a progressive ratio 3 (PR3) schedule of reinforcement. Separate rats were trained on an alcohol two-bottle choice paradigm with intermittent access. The GLP-1 agonist exendin-4 (Ex-4) was administered directly into the habenula to determine the effects on operant responding for palatable food as well as alcohol intake. Our results indicated that Ex-4 reliably suppressed PR3 responding and that this effect was dose-dependent. A similar suppressive effect on alcohol consumption was observed. These findings provide initial and compelling evidence that the habenula may mediate the inhibitory action of GLP-1 on reward, including operant and drug reward. Our findings further suggest that GLP-1 receptor mechanisms outside of the midbrain and ventral striatum are critically involved in brain reward neurotransmission.
文摘肥胖的形成和发展受生物、心理和社会因素的共同作用,其中食物奖赏对肥胖的产生有重要的作用。食物是一种自然奖赏,它指机体天生对食物的渴望和依赖。食物奖赏包括"wanting"、"liking"以及"learning&reinforcement"三个成分,每个成分由相应的神经通路表征。食物奖赏调控机体的摄食行为并以此调控体重变化。目前,关于肥胖与食物奖赏关系的理论模型主要有刺激—敏感化理论、奖赏过度理论以及奖赏不足理论。采用横断面设计、前瞻研究设计和纵向被试内重复测量设计,使用食物图片线索和直接给予美味奶昔的技术方法,人类脑成像研究从不同侧面为以上三个理论模型提供了证据。除此之外,食物奖赏还受基因的调控。目前,研究者关注较多的是多巴胺D2受体基因Taq IA rs1800497的多态性和FTO基因rs9939609的多态性对食物奖赏及体重改变的调控。
