[Pharmacotherapy for anorexia nervosa and bulimia nervosa]. / Pharmakotherapie von Anorexia nervosa und Bulimia nervosa: State of the Art.

Psychotherapy is the treatment of choice for both anorexia nervosa and for bulimia nervosa. However, many patients are also treated by pharmaceutical drugs. For the clinician it is difficult to choose pharmacotherapy, because the drugs may not be licensed, because of pharmacodynamic problems due to underweight or purging behaviour, or because of comorbidity. The present review summarises the current knowledge on pharmacotherapy for anorexia nervosa and bulimia nervosa considering the available guidelines. In general, the knowledge based on studies is insufficient for anorexia nervosa. Up to now, there is no proof of efficacy for any antidepressant or atypical antipsychotic with respect to weight gain; atypical antipsychotics may be helpful for ruminating or excessive motor hyperactivity. For bulimia nervosa antidepressants are the pharmacotherapy of first choice. Long-term effects, however, are still unknown.

A single episode of restraint stress regulates central corticotrophin- releasing hormone receptor expression and binding in specific areas of the mouse brain.

The importance of restraining stress-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) system within tolerable limits requires efficient mechanisms for feedback inhibition. Recently, central corticotrophin-releasing hormone (CRH) receptor type 1 (CRHR1) has been shown to mediate HPA system feedback inhibition. To date, most of the data regarding stress-associated expression changes of CRHR1 and CRHR2 mRNA and their ligand CRH have been generated in rats. Taken considerable species differences into consideration, and with the growing importance of transgenic mice, a systematic analysis of the time course of expression changes of CRH and its two receptors in the mouse brain is needed to provide more insight into the regulation of the HPA system, both under physiological and pathophysiological conditions in this species. We analysed in detail the time course of expression changes of CRH, CRHR1 and CRHR2 mRNA after of restraint stress in mice in stress-relevant brain regions (paraventricular nucleus, hippocampus, neocortex). We could show a rapid, strong and long-lasting decrease in cortical and hippocampal CRHR1 mRNA expression after stress, whereas CRHR2 mRNA increased in the same neuroanatomical areas. In situ hybridisation analyses could be further confirmed at the protein level by CRH receptor autoradiography with changes in CRH binding that persisted even 7 days after a single episode of restraint stress. Our observation that stress has opposing effects on CRHR1 and CRHR2 neuronal systems supports the idea that regulation of the relative contribution of the two CRH receptors to brain CRH pathways may be essential in coordinating physiological responses to stress. We further hypothesise that the sustained alteration of CRH receptor expression and binding after a single episode of stress could mediate the long-term effects of stress on neuroendocrine function and emotional regulation.

Persistent neuroendocrine and behavioral effects of a novel, etiologically relevant mouse paradigm for chronic social stress during adolescence.

Chronic stress is widely regarded as a key risk factor for a variety of diseases. A large number of paradigms have been used to induce chronic stress in rodents. However, many of these paradigms do not consider the etiology of human stress-associated disorders, where the stressors involved are mostly of social nature and the effects of the stress exposure persist even if the stressor is discontinued. In addition, many chronic stress paradigms are problematic with regard to stress adaptation, continuity, duration and applicability. Here we describe and validate a novel chronic social stress paradigm in male mice during adolescence. We demonstrate persistent effects of chronic social stress after 1 week of rest, including altered adrenal sensitivity, decreased expression of corticosteroid receptors in the hippocampus and increased anxiety. In addition, pharmacological treatments with the antidepressant paroxetine (SSRI) or with the corticotropin-releasing hormone receptor 1 antagonist DMP696 were able to prevent aversive long-term consequences of chronic social stress. In conclusion, this novel chronic stress paradigm results in persistent alterations of hypothalamus-pituitary-adrenal axis function and behavior, which are reversible by pharmacological treatment. Moreover, this paradigm allows to investigate the interaction of genetic susceptibility and environmental risk factors.