The Y of hYperactivitY in Anorexia Nervosa: Role of neuropeptide Y in hyperactivity associated with Anorexia Nervosa
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Anorexia Nervosa is a dramatic neuro-psychiatric disorder characterized by severe selective restriction of food intake, hypophagia and hypothermia but also behavioral hyperactivity. Behavioral hyperactivity aggravates the already serious food-deprived state of anorexia patients, hinders body-weight gain and increases the probability of relapse; therefore, it is an important target in the treatment of anorexia nervosa. The activity-based-anorexia (ABA) model of anorexia and is extensively used to investigate the underlying neurobiological systems involved in hyperactivity. The hypothalamus is considered the major brain site for regulation energy metabolism, because it can assess the immediate energy state of the organism and consists of several nuclei. These different nuclei communicate with each other by using neurotransmitters and neuropeptides. One of these neuropeptides is neuropeptide Y (NPY); it is considered to most potent orexigenic neuropeptide known and it heavily innervates the hypothalamic nuclei. This neuropeptide increases feeding behavior, is upregulated in response to food-deprivation and acts via its abundant, centrally spread Y1, Y2 and Y5 receptors. In anorexia patients, high levels of NPY have been found, however, these patients do not eat. This phenomenon is termed the “NPY-paradox”. In addition, most of these anorexia patients display high levels of physical activity, despite their severe state of emaciation. The aim of this thesis was to investigate the potential role through which NPY contributes to hyperactivity associated with anorexia nervosa. First the possible underlying neurobiological systems involved in this behavior were described. Second, the existing hypotheses about function of hyperactivity in anorexia were described. These hypotheses include, the “foraging hypothesis”, the “hypothermia hypothesis” and the “reward hypothesis”. Furthermore, the possible role of NPY in these hypotheses was investigated with special attention to the NPY receptors. Based on the evidence provided by recent studies the most appropriate hypothesis seems to be a combination of the “foraging hypothesis” and the “reward hypothesis”. The role of NPY in this combined hypothesis is that of activating the neuro-endocrine systems involved in foraging behavior, to down regulate thermogenesis and to activate reward pathways to reinforce this behavior adjacent to direct pathways affecting these mechanisms.