Evaluation of the effects of a diabetes type 2 rat model and semaglutide treatment on the sucrose preference test

Abstract

Diabetes type 2 (T2D) is the most common metabolic disorder worldwide and can be associated with eating disorders and/or depression. Recent evidence suggests that semaglutide, glucagon-like peptide 1 agonist and antidiabetic drug, may affect appetite, food preference, but also mood, although preclinical data are lacking or conflicting. We therefore investigated the effects of T2D model based on high-fat diet and streptozotocin administration in middle-aged rats and semaglutide treatment on anhedonia or binge eating. Sprague-Dawley rats of both sexes were fed high-fat or control diet and treated with streptozotocin or vehicle. When T2D model or control was developed, rats were treated or not with semaglutide/solvent. These animals were studied in separate cohorts subjected to behavioral battery including sucrose preference test. The main effects of model, sex and treatment were found to be significant for sucrose preference, with T2D rats, female rats and semaglutide-treated rats, respectively, with the former showing decreased and two latter increased levels compared to respective controls. In addition, the main effects of model and sex showed differences in sucrose intake per 100 g animal body mass (SI), with T2D and female animals, showing decreased and increased levels, respectively, compared to their respective controls. Our results showed that T2D rats had reduced sucrose intake compared to controls, which could be related to anhedonia, and SI seems to be a more appropriate parameter than sucrose preference for this model. Semaglutide treatment had no effect on this parameter, which emphasizes the importance of dietary changes in T2D and warrants further investigation