1. Dopamine D2/3 receptor antagonism reduces activity-based anorexia
- Author
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Stephanie J. Klenotich, Stephanie C. Dulawa, Matthew S. McMurray, Emily V. Ho, and C H Server
- Subjects
Olanzapine ,medicine.medical_specialty ,Anorexia Nervosa ,Indoles ,medicine.drug_class ,Atypical antipsychotic ,Anorexia ,Motor Activity ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Benzodiazepines ,Eating ,Mice ,0302 clinical medicine ,Eticlopride ,Piperidines ,Dopamine receptor D3 ,Internal medicine ,Dopamine receptor D2 ,Tetrahydroisoquinolines ,Hypophagia ,Nitriles ,Salicylamides ,Weight Loss ,medicine ,Animals ,Biological Psychiatry ,Mice, Inbred BALB C ,organic chemicals ,fungi ,Receptors, Dopamine D3 ,food and beverages ,030227 psychiatry ,3. Good health ,Psychiatry and Mental health ,Disease Models, Animal ,Dopamine D2 Receptor Antagonists ,Endocrinology ,Original Article ,Female ,medicine.symptom ,Amisulpride ,Sulpiride ,Psychology ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT2A/2C, 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted.
- Published
- 2015