Extended Data Fig. 9: Assessment of aversion in rodents.
From: GLP-1-directed NMDA receptor antagonism for obesity treatment
a-d, Chow-fed Wistar rats were dosed once-daily with s.c. injections of 100 nmol kg−1 MK-801 (n = 12 rats), 100 nmol kg−1 GLP-1 (n = 12 rats), 100 nmol kg−1 GLP-1–MK-801 (n = 12 rats) or vehicle (isotonic saline, n = 13 rats) for three consecutive days while being offered the voluntary choice between chow and kaolin (a non-food product). a, Schematic. b, Change in body weight. c, Cumulative food intake. One food monitor did not work for one mouse in vehicle group. d, Time-resolved kaolin intake. One datapoint in GLP-1–MK-801 was omitted due to extensive food spillage. e-h, Chow-fed Sprague-Dawley rats were dosed once-daily with s.c. injections of 100 nmol kg−1 MK-801 (n = 8 rats), 100 nmol kg−1 GLP-1 (n = 8 rats), 100 nmol kg−1 GLP-1–MK-801 (n = 8 rats) or vehicle (isotonic saline, n = 8 rats) for three consecutive days while being offered the choice between chow and kaolin. e, Schematic. f, Change in body weight. g, Cumulative food intake. h, Cumulative kaolin intake. Two data points were omitted from analysis in vehicle group due to extensive food spillage. i-m, Wheel running study investigating aversive behaviour in response to treatment. Lean chow-fed male C57BL/6 J mice were single-housed in cages equipped with a running wheel and allowed 3 days of habituation before being treated with once-daily s.c. injections of 100 nmol kg−1 GLP-1–MK-801 (n = 8 mice), 10 nmol kg−1 semaglutide (n = 8 mice) or vehicle (isotonic saline, n = 7 mice) for 5 days with daily measurements of running distance at the time of injection. One mouse in vehicle group was excluded from analysis due to sickness. i, Schematic. j, Change in body weight. k, Cumulative food intake. l, Daily running wheel distance during habituation and treatment period. One datapoint in vehicle group was excluded due to the running wheel got stuck between day -1 to day 0. m, Cumulative running wheel distance during treatment period. Data analysed by two-way repeated measures ANOVA to assess main effect effects of treatment (b, c, f, g, j, k and m) and two-way ANOVA, multiple comparison, Bonferroni post hoc test (h). Data represents mean ± SEM; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Detailed statistics are in Supplementary Table 1. The diagrams in a, e and i were created using BioRender.