The demyelinating agent cuprizone induces a male-specific reduction in binge eating in the binge-prone C57BL/6NJ strain

Richard K. Babbs; Jacob A. Beierle; Julia C. Kelliher; Rose Medeiros; Jeya Anandakumar; Anyaa Shah; Emily J. Yao; Melanie M. Chen; Camron D. Bryant

When considering the female and male datasets separately, females showed significant 231 weight loss earlier on at D4 and D5 (Fig.2B) and both sexes showed a significant reduction in 232 body weight from D8-D14, after which there was recovery of weight loss within 24 following 233 removal of the cuprizone diet and replacement with normal home cage chow (Fig.2B,C) . 234 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/865600 doi: bioRxiv preprint Cuprizone treatment reduces BE and compulsive-like eating in male but not female mice 235 of the BE-prone B6NJ substrain 236 Consistent with our previous report (Kirkpatrick et al., 2017) , B6NJ mice showed greater 237 overall PF consumption compared to B6J mice (Fig.3 ) -a behavior that we previously showed 238 was associated with an enrichment of downregulated genes involved in myelination in the striatum 239 (Kirkpatrick et al., 2017) . However, contrary to our hypothesis that the demyelinating agent 240 cuprizone would increase BE, prior treatment with cuprizone in the BE-prone B6NJ substrain 241 actually decreased the amount of PF intake and decreased the slope of escalation in PF intake 242 intake across days (Fig.3A,B) . Despite the lack of effect of cuprizone on the amount of PF intake 246 in B6J mice, cuprizone induced a small but significant non-zero slope in escalation of PF intake 247 across days (Fig.3B ). In examining compulsive-like PF intake in the light/dark conflict test on D23, 248 as expected, the BE-prone B6NJ strain showed a significant increase in PF intake relative to the 249 BE-resistant B6J strain; however, there was no effect of cuprizone or interaction with substrain in 250 the sex-combined dataset (Fig.3C) . 251