Characterization of Weight Gain and Motivation for Palatable Food in MAGEL2‐Deficient Rats

Abstract

Disrupting expression of MAGEL2, part of the MAGE family, is associated with disorders such as Prader‐Willi syndrome (PWS). PWS involves changes to energy balance including hyperphagia and weight gain, but the neurohormonal mechanisms underlying these changes have not been fully elucidated. As energy balance is controlled by the central nervous system, rodent models represent an important tool in understanding the neurobiology of PWS and how gene expression changes such as MAGEL2 disruption may impact feeding, weight gain, and motivation for food. Here, we used a novel MAGEL2‐deficient rat to examine how disruption of MAGEL2 expression impacts weight gain and motivation for palatable food. We hypothesized that MAGEL2‐deficient rats would have increased body weight post‐weaning and would exhibit increased motivation to obtain palatable food. Ongoing studies suggest that, contrary to our hypothesis, MAGEL2‐deficient rats weigh less than wild type controls in the 6 weeks after weaning (p<0.05). When wild type and MAGEL2‐deficient rats were trained to lever press for a palatable sucrose solution or fat solution on a progressive ratio (PR) schedule of reinforcement, no significant genotype differences were observed for active lever responses, reinforcers earned, or breakpoint for sucrose self‐administration. For fat self‐administration, no significant effects of genotype were observed on these measures in the first day of PR testing; on a second day of PR testing, MAGEL2‐deficient rats had a lower breakpoint than did wild type counterparts (p<0.05), suggesting that they do not exhibit greater motivation to work for fat solution and may in fact be less motivated to obtain this palatable food compared to wild type rats. Interestingly, in ad libitum feeding studies, more MAGEL2‐deficient rats exhibited food hoarding than did wild type controls (p<0.05). Other studies in our lab are continuing to investigate meal patterns and palatable fluid intake in the MAGEL2‐deficient rat model. Collectively, these findings suggest that the MAGEL2‐deficient rat may be useful for assessing mechanisms of hoarding behavior in PWS, but may be less useful for examining the underpinnings of PWS‐associated weight gain as the MAGEL2‐deficient rat does not exhibit increased body weight like humans with PWS.