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大鼠的 Roux-en-Y 胃旁路手术增加了蔗糖味觉相关的动机行为,而不依赖于药理学 GLP-1 受体调节。

Roux-en-Y gastric bypass in rats increases sucrose taste-related motivated behavior independent of pharmacological GLP-1-receptor modulation.

机构信息

Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306-4301,USA.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2012 Mar 15;302(6):R751-67. doi: 10.1152/ajpregu.00214.2011. Epub 2011 Dec 14.

Abstract

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30 μg/kg), agonist exendin-4 (1 μg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.

摘要

胃旁路手术(RYGB)已被证明可降低大鼠对高蔗糖浓度的摄取反应性,而胰高血糖素样肽-1 受体(GLP-1R)的基因缺失已被证明可降低小鼠对低蔗糖浓度的摄取反应性。在这里,我们评估了 RYGB 和药理学 GLP-1R 调节对给予标准饮食的大鼠在短暂访问测试中的蔗糖舔舐的影响,该测试评估了摄取和食欲行为。在手术前和手术后禁食以及手术后非禁食期间以及腹腔内注射 GLP-1R 拮抗剂 exendin-3(9-39)(30 μg/kg)、激动剂 exendin-4(1 μg/kg)和载体 30 分钟后,对大鼠进行测试分钟,在此期间,在 10 秒试验中呈现蔗糖浓度系列(0.01-1.0 M)。其他大鼠在手术后或肽或载体注射后 15 分钟,在禁食和非禁食时进行测试。无论食物剥夺状态、蔗糖经验或 GLP-1R 调节如何,RYGB 大鼠的试验次数是假手术大鼠的 1.5-3 倍,表明食欲行为增加。在非禁食条件下,具有术前蔗糖经验的 RYGB 大鼠相对于水舔食更多的蔗糖,而相对于假手术大鼠。Exendin-4 和 exendin-3(9-39) 在单瓶测试中影响 0.3 M 蔗糖摄入,但从未与手术组相互作用影响短暂访问反应。与之前在接受 RYGB 和 GLP-1R 基因敲除的肥胖和相对较瘦的大鼠以及 GLP-1R 基因敲除的小鼠的报告不同,我们发现 RYGB 或 GLP-1R 阻断都不会降低我们的非肥胖标准饮食大鼠对蔗糖的摄取反应性。总的来说,这些结果强调了这样一个事实,即在 RYGB 和/或 GLP-1R 调节后,对蔗糖的味觉驱动动机行为的变化非常依赖于模型和测量。

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