Neurobiological parameters and anorexia nervosa: Findings from animal studies

Abstract

Although anorexia nervosa (AN) was already described in the 19th century, its etiology remains unclear. Animal models may help to advance our knowledge on AN. The rat activity-based anorexia (ABA) model, which consists of scheduled feeding along with running wheel access (RWA), mimics the starvation and physical hyperactivity of AN patients. Following introduction of a feeding schedule (1–2 h/d), rats further reduce food intake, become hyperactive, and lose body weight. The aim of this translational work was to identify neurobiological parameters associated with the development of ABA. Circulating metabolic fuels and hormones, hypothalamic gene expression, and behavioural responses to icv leptin infusion were investigated in ABA rats and appropriate controls. Rats showed marked, but expected, changes in circulating metabolic fuels (e.g. glucose, β-hydroxybutyrate) and hormones (e.g. leptin, insulin) during development of ABA. Hypothalamic POMC and CART mRNA levels were decreased in ABA rats, whereas AgRP and NPY mRNA levels were increased. Expression of second-order neuropeptides, e.g. CRH, prepro-orexin, was not changed. Chronic icv infusion of leptin, acting upstream of POMC/CART and NPY/AgRP neurons, decreased food intake as well as RWA in ABA rats, discordant to earlier results of melanocortin (ant)agonist infusions. These results warrant further research on the role of the (extra)hypothalamic leptin pathway in the development of ABA. Meanwhile the relevance of these preclinical data is investigated in clinical studies by studying the relation between plasma leptin levels and physical activity in AN patients.