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. 2024 May 15;629(8014):1133–1141. doi: 10.1038/s41586-024-07419-8

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 9 — 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.

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