The effect of the demyelinating agent cuprizone on binge-like eating of sweetened palatable food in female and male C57BL/6 substrains

Abstract

Binge eating is a heritable symptom of eating disorders with an unknown genetic etiology. Rodent models for binge-like eating (BLE) of palatable food permit the study of genetic and biological mechanisms. We previously genetically mapped a coding mutation in Cyfip2 associated with increased BLE of sweetened palatable food in the C57BL/6NJ versus C57BL/6J substrain. The increase in BLE in C57BL/6NJ mice was associated with a decrease in transcription of genes enriched for myelination in the striatum. Here, we tested the hypothesis that decreasing myelin levels with the demyelinating agent cuprizone would enhance BLE. Mice were treated with a 0.3% cuprizone home cage diet for two weeks. Cuprizone induced similar weight loss in both substrains and sexes that recovered within 48 h after removal of cuprizone. Following a three-week recovery period, mice were trained for BLE in an intermittent, limited access procedure. Surprisingly, cuprizone significantly reduced BLE in male but not female C57BL/6NJ mice while having no effect in C57BL/6J mice. Cuprizone also reduced myelin basic protein (MBP) at seven weeks post-cuprizone removal while having no effect on myelin-associated glycoprotein at this time point. C57BL/6NJ mice also showed less MBP than C57BL/6J mice. There were no statistical interactions of Treatment with Sex on MBP levels, indicating that differences in MBP reduction are unlikely to account for sex differences in BLE. To summarize, cuprizone induced an unexpected, significant reduction in BLE in C57BL/6NJ males, which could indicate genotype-dependent sex differences in the biological mechanisms of BLE.

Keywords: Binge eating disorder; Demyelination; QTL; Reduced complexity cross; Sex as a biological variable; Sex differences.