On the role of dopamine in the pathophysiology of anorexia nervosa

the Study Group on Anorexia Nervosa (AN): Basic Mechanisms, Clinical Approaches and Treatment met in Geneva, Switzerland to discuss recent progress in research on anorexia nervosa, and to identify directions for future studies. Anorexia nervosa is a disorder of unknown etiology, without a specific curative treatment, affecting mostly individuals in adolescence and early adulthood, with significant morbidity and mortality, and having a major impact on psychosocial and vocational development. In anorexia nervosa there are severe disturbances in virtually every endocrine system, such as the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, the hypothalamic-pituitary-thyroid (HPT) axis, the growth hormone (GH)lsomatomedin C (IGF-1) system, and the central and peripheral arginine vasopressin (AVP) systems. Furthermore, classical neurotransmitter systems, such as the cholinergic noradrenergic, and serotonergic systems, are abnormally regulated in anorexia nervosa. New research data is also emerging on the abnor-maUregulation of immune function in this disorder. The Study Group concluded that even though several biological systems are abnormally regulated in anorexia nervosa, there is no biological test which is specific enough to make the diagnosis of the disorder. New directions for research in anorexia nervosa are identified and discussed in this report. Finally, the Study Group proposed future meetings to bring together clinical and pre-clinical (pharmacological, biochemical, and molecular) scientists studying topics, such as neuroendocrine function, which are important in the biology of anorexia nen/osa.

British journal of pharmacology, 2014

Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5-HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5-HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5-HT(2C/2A) receptors, have been related to the pathophysiology of AN in hu...

Biological Psychiatry, 2005

Background: Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). Methods: To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [ 11 C]raclopride was used to assess DA D2/D3 receptor binding. Results: The women who were recovered from AN had significantly higher [ 11 C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [ 11 C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. Conclusions: These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.

Psychiatry Research: Neuroimaging, 2015

The neurobiology of anorexia nervosa remains incompletely understood. Here we utilized PET imaging with the radiotracer [ 11 C]raclopride to measure striatal dopamine type 2 (D 2) receptor availability in patients with anorexia nervosa. 25 women with anorexia nervosa who were receiving treatment in an inpatient program participated, as well as 25 control subjects. Patients were scanned up to two times with the PET tracer [ 11 C]raclopride: once while underweight, and once upon weight restoration. Control subjects underwent one PET scan. In the primary analyses, there were no significant differences between underweight patients (n=21) and control subjects (n=25) in striatal D 2 receptor binding potential. Analysis of subregions (sensorimotor striatum, associative striatum, limbic striatum) did not reveal differences between groups. In patients completing both scans (n=15), there were no detectable changes in striatal D 2 receptor binding potential after weight restoration. In this sample, there were no differences in striatal D 2 receptor binding potential between patients with anorexia nervosa and control subjects. Weight restoration was not associated with a change in striatal D 2 receptor binding. These findings suggest that disturbances in reward processing in this disorder are not attributable to abnormal D 2 receptor characteristics, and that other reward-related neural targets may be of greater relevance.

Pharmacology Biochemistry and Behavior, 1988

of the role of dopamine in amphetamine anorexia. PHARMACOL BIOCHEM BEHAV 30(3) [641][642][643][644][645][646][647][648] 1988.--A microstructural analysis paradigm was used to study amphetamine anorexia. Doses above 0.40 mg/kg significantly reduced food intake by reducing eating time; in contrast, eating rate was increased at these doses. Examination of the frequency distribution ofinterresponse times (IRTs) revealed a significant shift to shorter IRTs at doses as low as 0.125 mg/kg. Pimozide blocked amphetamine anorexia at 0.5 and 1.0 mg/kg, suggesting that at both doses amphetamine anorexia has a dopaminergic substrate. However, the atypical neuroleptic thioridazine did not antagonize amphetamine. Furthermore, effects of amphetamine were additive with those of apomorphine, administered at a dose known to suppress feeding by inhibiting mesolimbic DA neurons. These results provide evidence against an involvement of the mesolimbic DA system in amphetamine anorexia.

Psychological Medicine, 1974

SYNOPSIS Recent work on the central mechanisms of food intake is reviewed in relation to anorexia nervosa. On the basis of the present review a number of conclusions are drawn as possible avenues for future research. A proposal is outlined for the investigation of L-dopa as a potential treatment for anorexia nervosa.

Anorexia nervosa is a rare, yet dangerous and often deadly disorder that primarily affects young teenage women. Individuals with anorexia are driven to starvation, refuse to maintain a minimally normal body weight, posses distorted perceptions and beliefs of oneself, and demonstrate abnormal attitudes toward food and weight. Specifically the restricting type, a subtype of anorexia that does not involve binging or purging behavior, will be the focus of this paper. Within the anorexic brain there are many chemical changes and brain abnormalities that take place including hormonal and chemical imbalances and dysfunction in the insular cortex and frontal-striatal circuits. Many of these abnormalities are believed to intensify and prolong the duration of the disorder while others are a direct result of starvation. Medications provide some relief for certain symptoms of anorexia, but the most successful treatment options include forms of CBT and family therapy.

European Journal of Pharmacology, 2003

Eating disorders, i.e. anorexia and bulimia nervosa, are disorders of eating behavior and body weight regulation. Most likely because there are few, if any, effective treatments, eating disorders are considered to be chronic disorders interrupted only by intermittent periods of shortlived remission. The neurobiology of eating, most of which explores hypothalamic mechanisms, has had no influence on the treatment of eating disorders, with the exception of psychopharmacology. However, while most patients are treated with psychoactive drugs, there is no evidence that these are effective. This may be because pharmacological attempts so far have targeted the wrong symptoms. We review the symptomatology of anorexia and bulimia and the outcome of presently used interventions. Everybody agrees that outcome must improve and to attack this clinical problem, we suggest a neurobiologically plausible framework for how the disorders develop and how they are maintained and outline a method of treatment and its results. D

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2007

Frontiers in Neuroendocrinology, 2008

The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.