Interaction Between Genetic And Environmental Factors Promotes Eating Disorders Altering Expression And Function Of Dopamine, Serotonin And Norepinephrine Receptors

Eating disorders are multifactorial conditions involving genetic, metabolic, environmental, and behavioral factors. Although animal studies cannot reproduce the complex psychosomatic features of human eating disorders, can be useful to separately examine the elements of the homeostatic and motivational impairments associated with compulsive eating behaviors. Drugs of abuse and palatable food intake show behavioral similarities and common neurobiological adaptations have been proposed to be involved in both drug and food related-disorders (Volkow and Wise, 2005). Compulsive drug intake in the face of adverse consequences is a hallmark feature of addiction and compulsive drug seeking has been shown to emerge only following an extended history of drug-taking (Vanderschuren and Everitt, 2004). Similarly, compulsive eating emerges following extended access to a palatable diet (Johnson and Kenny, 2010). Finally, stress exposure influences both the propensity to take drugs and food intake. Dopamine is a neurotransmitter critically involved in the reward and motivational aspects of feeding and D2 receptors have received particular attention (Wang et al., 2001; Davis et al 2009). However, recent reviews have focused on central monoamine systems in eating disorders, such serotonin and norepinephrine (Hainer et al , 2006; Kaye, 2008). Here we show that interaction between extended access to chocolate and chronic stress is able to transform adaptive food seeking/intake behavior into compulsive eating in DBA/2J mice (previously shown by Patel and coworkers, 2006, to be characterized by high impulsivity), but not in C57BL/6J mice. Moreover, we find strong alterations of dopamine, serotonin and norepinephrine receptors expression in three brain areas (medial prefrontal cortex, nucleus accumbens, dorsal striatum) critically involved in food-related motivated behavior. The animal model proposed here could be a good tool for understanding how environmental factors interact with genetic vulnerability to promote the development of eating disorders altering expression and function of dopamine, serotonin and norepinephrine receptors