Anorexia nervosa (AN), mostly observed in female adolescents, is the most fatal mental illness. Its core is a motivational imbalance between exercise and feeding in favour of the former. Although several animal models of AN have been proposed, none of them specifically assesses the motivation for exercise and/or feeding. In keeping with this issue, we recently developed an operant conditioning-based model wherein motivation for each of these two rewards can be examined singly or within a choice setting in mice [1Muguruza, et al. JCI Insight 2019 ;  4 (5) : 126190

Cliquez ici pour aller à la section Références]. By means of this model, we have recently examined whether infant-early adolescent stress (post-weaning social isolation), one precipitating factor in AN, affects in a sex-dependent manner the reinforcing values of either reward [2Hurel, et al. Front Pharmacol 2019 ;  10 : 587

Cliquez ici pour aller à la section Références].

Stressed and control male/female C57Bl/6N mice were exposed, when 5-weeks old, to a cued-reward motivated instrumental task wherein wheel-running sequences and palatable food pellets, each reward provided singly, were conditioned by nose-poke responses. These responses obeyed fixed ratio (FR) reinforcement schedules for 10 sessions before being tested under a progressive ratio (PR) schedule of reinforcement for one session. Thereafter, mice underwent 10 FR sessions wherein they had the choice between either reward, the last 5 sessions being performed under food restriction conditions. Infant-adolescent stress, which began at postnatal day 22 (first postweaning day), consisted in individual housing, as compared to controls, which were all collectively housed (3/cage).

Whether wheel-running and palatable food were provided separately or within a choice paradigm, post-weaning isolation-reared males responded to similar extents for each reward when the three other mouse groups displayed increased responding for wheel-running. The negative impact of the early stressor on male nose poke responding for wheel-running, compared to that measured in the other mouse groups, extended to the running performance during each rewarded sequence (i.e. reward consumption). When food-restricted, motivation for food overpassed progressively that for running in all groups, with females reaching higher levels than males.

Although the stress model that we used did not trigger a sex-dependent imbalance between exercise and feeding drives that would be reminiscent of what is observed in anorectic girls, we believe that the quest for other stress models, possibly combined with genetics, could prove fruitful to model some endophenotypic traits of AN.