Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA.
Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA.
Physiol Behav. 2023 Apr 1;262:114093. doi: 10.1016/j.physbeh.2023.114093. Epub 2023 Jan 24.
Eating and drinking co-occur and many of the same mechanisms that control one are involved in the control of the other, making it difficult to isolate specific mechanisms for the control of fluid intake. Glucagon-like peptide-1 (GLP-1) is a peptide that seems to be involved in the endogenous control of both ingestive behaviors, but we lack a thorough understanding of how and where GLP-1 is acting to control fluid intake. Vasopressin-deficient Brattleboro rats are a model of hereditary hypothalamic diabetes insipidus that have been used extensively for the study of vasopressin actions in behavior and physiology. Here, we propose that these rats, that eat normally but drink excessively, provide a useful model to dissociate central controls of food and fluid intakes. As an initial step toward establishing this model for these purposes, we focused on GLP-1. Similar to the effect observed after treatment with a GLP-1 receptor (GLP-1R) agonist, the intake difference between wildtype and Brattleboro rats was largely a function in the number of licking bursts, indicating differences in post-ingestive feedback (e.g., satiation). When given central injections of a GLP-1R agonist, the effect on feeding was comparable between wildtype and Brattleboro rats, but the effect of drug on fluid intake was markedly exaggerated in Brattleboro rats. Additionally, Brattleboro rats did not respond to GLP-1R antagonism, whereas wildtype rats did. Taken together, these results suggest that Brattleboro rats exhibit a selective disruption to GLP-1's control of water intake. Overall, these experiments provide foundational studies of the ingestive behavior of Brattleboro rats and demonstrate the potential to use these rats to disentangle the effects of GLP-1 on food and fluid intakes.
进食和饮水同时发生，许多控制一种行为的机制也参与控制另一种行为，这使得很难分离出专门用于控制液体摄入的特定机制。胰高血糖素样肽-1（GLP-1）是一种似乎参与了摄食行为内源性控制的肽，但我们对 GLP-1 如何以及在何处发挥作用以控制液体摄入缺乏全面的了解。血管加压素缺乏性 Brattleboro 大鼠是遗传性下丘脑性尿崩症的模型，已广泛用于研究血管加压素在行为和生理学中的作用。在这里，我们提出这些正常进食但过度饮水的大鼠提供了一个有用的模型，可以将食物和液体摄入的中枢控制分开。作为为此目的建立该模型的初步步骤，我们专注于 GLP-1。类似于用 GLP-1 受体（GLP-1R）激动剂治疗后观察到的效果，野生型和 Brattleboro 大鼠之间的摄入量差异主要是由于舔食爆发的数量不同，这表明在摄食后反馈（例如，饱腹感）方面存在差异。当给予中枢注射 GLP-1R 激动剂时，野生型和 Brattleboro 大鼠的摄食效应相当，但药物对液体摄入的影响在 Brattleboro 大鼠中明显夸大。此外，Brattleboro 大鼠对 GLP-1R 拮抗作用没有反应，而野生型大鼠则有反应。总之，这些结果表明 Brattleboro 大鼠表现出 GLP-1 对水摄入控制的选择性破坏。总的来说，这些实验提供了 Brattleboro 大鼠摄食行为的基础研究，并证明了使用这些大鼠来分离 GLP-1 对食物和液体摄入的影响的潜力。
