Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, H181, Hershey, PA 17033.
Physiol Behav. 2021 Feb 1;229:113279. doi: 10.1016/j.physbeh.2020.113279. Epub 2020 Dec 5.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is essential for the regulation of food intake and approved for the treatment of type 2 diabetes mellitus and obesity in humans. More recently, GLP-1 has been investigated for its ability to modulate motivation for food and drugs. Reward behavior can be divided into two components: 'motivational' (i.e., approach and consummatory behaviors) and 'affective' (i.e., perceived palatability). Studies show that GLP-1 analogs reduce the motivation to approach and consume palatable food, but the impact on affective responding is unknown. Thus, the present study tested the effect of the GLP-1 analog, Exendin-4 (Ex-4), on the appetitive response to intraorally delivered sucrose and quinine. Results showed that Ex-4 (2.4ug/kg ip) failed to alter passive drip, appetitive reactions (i.e., mouth movements, tongue protrusions, and lateral tongue protrusions) or aversive reactions (i.e., gapes) to sucrose. Paw-licking, however, was significantly reduced by Ex-4. Treatment with Ex-4 also failed to influence passive drip to quinine, but increased the latency to gape and reduced the total number of gapes emitted. In addition, Ex-4 reduced intake of quinine in water restricted rats, but did not reduce conditioned aversion (i.e., gapes) or avoidance (i.e., reduced intake) of a LiCl-paired saccharin cue. Thus, while Ex-4 had no effect on a learned aversion, it reduced approach and ingestion of sweet and bitter solutions, while leaving the appetitive affective response to the sweet almost intact, and the aversive affective response to the bitter reduced. Treatment with Ex-4, then, differentially modulates appetitive and consummatory components of reward, depending on the valence of the stimulus and whether its valence is learned or innate.
胰高血糖素样肽-1 (GLP-1) 是一种肠促胰岛素激素，对调节食物摄入至关重要，已被批准用于人类 2 型糖尿病和肥胖症的治疗。最近，GLP-1 因其调节食物和药物动机的能力而受到研究。奖励行为可分为两个组成部分：“动机”（即接近和消费行为）和“情感”（即感知的美味）。研究表明，GLP-1 类似物可降低对美味食物的接近和消费动机，但对情感反应的影响尚不清楚。因此，本研究测试了 GLP-1 类似物 Exendin-4 (Ex-4) 对口服给予蔗糖和奎宁的食欲反应的影响。结果表明，Ex-4（2.4ug/kg ip）并未改变被动滴注、食欲反应（即口部运动、舌头伸出和舌头侧向伸出）或对蔗糖的厌恶反应（即张口）。然而，爪子舔舐行为明显减少。用 Ex-4 治疗也未能影响对奎宁的被动滴注，但增加了张口潜伏期并减少了张口总数。此外，Ex-4 减少了水限制大鼠对奎宁的摄入，但并未减少条件性厌恶（即张口）或回避（即减少对蔗糖的摄入）对配对的蔗糖提示。因此，虽然 Ex-4 对已习得的厌恶无影响，但它降低了对甜味和苦味溶液的接近和摄入，同时使对甜味的食欲情感反应几乎保持不变，而对苦味的厌恶情感反应降低。因此，Ex-4 的治疗可根据刺激的效价以及其效价是否为学习或先天的，差异调节奖励的食欲和消费成分。
