David Sydney A, Brakey Destiny J, Paul Matthew J, Daniels Derek
Department of Psychology, the State University of New York at Buffalo, Buffalo, NY USA.
Department of Psychology, the State University of New York at Buffalo, Buffalo, NY USA; Department of Biological Sciences, the State University of New York at Buffalo, Buffalo, NY USA.
Physiol Behav. 2025 Sep 1;298:114958. doi: 10.1016/j.physbeh.2025.114958. Epub 2025 May 22.
Food and fluid intakes are physiologically and behaviorally intertwined; one often affects the other. Likewise, pharmacological manipulations that influence eating often affect drinking. For example, glucagon-like peptide-1 (GLP-1) suppresses both eating and fluid intake, but the respective elements of the GLP-1 system remain unparsed. The Brattleboro rat has emerged as a model to test for separable elements in the control of fluid or food intake. Brattleboro rats have hereditary hypothalamic vasopressin deficiency. To compensate for the resultant polyuria, they drink copious amounts of water. Eating, however, is similar to that observed in wildtype littermates and other Long Evans rats. Interestingly, treatment with a GLP-1 receptor agonist exendin-4 (Ex4) causes an exaggerated suppression of drinking in Brattleboro rats, but suppression of eating is comparable to wildtype controls. To test if this hyper-responsivity depends on the polydipsia in these rats, we normalized their drinking using desmopressin (ddAVP), a V2R agonist, before treatment with Ex4. ddAVP attenuated, but did not completely prevent, the hyper-responsivity to Ex4. Conversely, we treated wildtype rats with acute or chronic tolvaptan, a V2R antagonist, which generated a Brattleboro-like polydipsia, but this did not recapitulate the hyper-responsivity to Ex4 observed in Brattleboro rats. Based on these results, we conclude that polydipsia alone is insufficient to generate a hyper-responsive fluid intake suppression by Ex4, and that Brattleboro rats have at least some persistent hyper-responsivity to Ex4, even after alleviation of their polydipsia. These results provide important context for future studies using Brattleboro rats to study the GLP-1 system.
食物和液体摄入在生理和行为上相互交织；二者常常相互影响。同样，影响进食的药理学操作通常也会影响饮水。例如，胰高血糖素样肽-1（GLP-1）会抑制进食和液体摄入，但GLP-1系统的各个组成部分仍未得到解析。布拉德福德大鼠已成为测试液体或食物摄入控制中可分离成分的模型。布拉德福德大鼠患有遗传性下丘脑血管加压素缺乏症。为了补偿由此导致的多尿，它们会大量饮水。然而，它们的进食情况与野生型同窝大鼠和其他长 Evans 大鼠相似。有趣的是，用GLP-1受体激动剂艾塞那肽-4（Ex4）治疗会导致布拉德福德大鼠的饮水受到过度抑制，但进食抑制情况与野生型对照相当。为了测试这种高反应性是否取决于这些大鼠的多饮情况，我们在使用Ex4治疗前，用去氨加压素（ddAVP，一种V2R激动剂）使它们的饮水正常化。ddAVP减轻了，但并未完全阻止对Ex4的高反应性。相反，我们用V2R拮抗剂托伐普坦对野生型大鼠进行急性或慢性治疗，这产生了类似布拉德福德大鼠的多饮情况，但这并未重现布拉德福德大鼠中观察到的对Ex4的高反应性。基于这些结果，我们得出结论，仅多饮不足以导致Ex4对液体摄入产生高反应性抑制，并且即使在缓解多饮后，布拉德福德大鼠对Ex4仍至少存在一些持续的高反应性。这些结果为未来使用布拉德福德大鼠研究GLP-1系统的研究提供了重要背景。
