|PI of the laboratory: Benjamin Boutrel |
(phone + E-Mail address) 021 643 69 47, Benjamin.Boutrel@chuv.ch
Direct supervisor (assistant): Clara Rossetti
(phone + E-Mail address): 021 643 69 44, Clara.Rossetti@chuv.ch
Department: DP-CHUV, Centre de Neurosciences Psychiatriques
Address: Site de Cery, 1008 Prilly
Role of the hypocretin/orexin system in the etiology of eating disorders in mice
Description of project:
Eating disorders are tragic and debilitating disorders that most commonly begins during adolescence in women and rises at alarming rates in industrialized countries (Kaye et al, 2009). These disorders usually begin with “harmless” efforts at dieting which then get out of control. There are two principal clinical types, restrictive and binge/purging. Anorexia Nervosa (AN) is characterized by an excessive dieting associated with a distorted image of the body and a morbid fear of weight gain. Bulimia nervosa (BN) is characterized by binge eating (loss of control over food intake) and compensatory purging by vomiting, use of laxatives, diuretics or diet pills, exercise and fasting. The etiology of eating disorders remains currently unknown, but evidence suggests multifactorial causes based on culture, environment, biology and genetic predisposition. Eating disorders involve psychological and physiological antecedents which can not be limited to an impairment of brain pathways involved in the regulation of metabolic needs. In clinical practice, anorexic patients often report stress as a primary trigger for their eating disorders. Further, patients often report their deprivation as a dependency, like an overpowering addiction in which they feel trapped within their own prison and can not get out. Our hypothesis is that this dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways involving the orexin/hypocretin system (Sakurai, 2007).
Until recently, animal models of voluntary food restriction remained unavailable. However, intermittent access to highly preferred food has been shown to induce behavioral adaptations in rats that were similar to those observed in patients with eating disorders regarding consummatory, anxiety-related and metabolic effects of dieting (Cottone et al., 2008, 2009).
Question / Aim of the work:
The aim of this project is to reproduce the above mentioned paradigm in rats and to adapt it to transgenic mice deficient in hypocretin/orexin and wild type littermates (male and female), in order to evaluate consequences of such a diet cycling procedure on behavior and brain adaptations.
Techniques / methods applied:
Behavioral characterization includes operant conditioning for food reward (to assess motivation for reward seeking and taking), evaluation of anxiety-like behaviors with an elevated plus maze (completed with corticosterone assays), evaluation of social interaction and novelty seeking in rats and mice. Further investigations of serotonergic adaptations in the brain may be suggested using classical molecular tools.
Cottone P, Sabino V, Steardo L, Zorrilla EP (2008) Intermittent access to preferred food reduces the reinforcing efficacy of chow in rats. Am J Physiol Regul Integr Comp Physiol. 295:R1066-76.
Cottone P, Sabino V, Steardo L, Zorrilla EP (2009) Consummatory, anxiety-related and metabolic adaptations in female rats with alternating access to preferred food. Psychoneuroendocrinology 34:38-49.
Kaye WH, Fudge JL, Paulus M (2009) New insights into symptoms and neurocircuit function of anorexia nervosa. Nat Rev Neurosci 10:573-84.
Sakurai T (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8:171-81
Link to the group web site