L'effetto sessualmente dimorfico della separazione materna su ratti anoressici

The anorexia nervosa (AN) is an eating disorder characterized by restricted food intake, a significant body weight loss and, commonly, an excessive physical activity. All these core symptoms of AN (i.e. deprivation of food and hyperactivity) can be mimicked by the rodent model of activity-based anorexia (ABA), which provides 23 hours on running wheel and 1 hour of access to a restricted amount of food. The ABA rats show an enhanced activity, self-starvation and weight loss like the anorexic patients. Furthermore, the investigations of the reason of the AN's onset highlights that the neonatal period and the maternal cares play a key roles in the pathogenesis of AN. In fact, the maternal deprivation during the neonatal period may influences the development of behavioral styles of patients with eating disorders, including AN. Previous experimental data have shown that the Maternal Separation (MS) produces in adolescent rats (and not in the adults) an anticipated onset of eating disorder. However, these studies did not deeply analyse the overall behavior of rats, especially regard of anxiety-like and stress behaviors, which are usually correlated with AN. In our experiment, we used a mild-stress ABA protocol, in which male and female adolescent rats have access to the wheel to run for two hours a day and a limited access to food for one hour a day (feeding test). This kind of protocol is chosen to not exacerbate the stress imposed to the animal, because some groups are also subjected to the MS. In particular, to study the onset of the pathology we analysed the body weight loss in relationship with activity on the running wheel and with the quantity of food consumed during the feeding test. We found out that, in general, the loss of body weight during ABA protocol is greater and faster in males than in females. Moreover, the MS induces a sexually dimorphic effect, because the anorexic males separated from their mother are more susceptible than the non-handling ABA males, while, in females, the maternal separation leads to hyperactivity the anorexic rats. Furthermore, the behavioral tests performed (the open field and the elevated plus maze) show that the ABA treatment causes that rats are more physically active, less anxious and more explorative. However, there is a further effect given by the MS: anorexic deprived affectively females show an even more hyperactive and less anxious behavior than ABA females, while, in males, the maternal separation induces animals to be more anxious than control groups. At last, to understand the reason why rats maintained the anorexic phenotypes, we consider the strong influence of the physical activity on the reward system, considering the dopaminergic system in the VTA and the serotonergic systems in the DRN. In fact, the human AN phenotype is characterized by a strong satisfaction for thinness and hyperactivity in the anorexic patients. In the anorexic rats, the two systems considered for reward circuits show a high sex-specificity: the dopaminergic system increases in ABA males, while the serotonergic system enhances in ABA females. In conclusion, these results indicate that the MS induces hyperactivity in females and more anxious-like behaviors in males. This study may have a translational implication for better understanding the role of early environment in the pathogenesis of AN.