Dopamine D2/3 receptor antagonism reduces activity-based anorexia.
SJ Klenotich
EV Ho
MS McMurray
CH Server
SC Dulawa
10027/20266
https://indigo.uic.edu/articles/journal_contribution/Dopamine_D2_3_receptor_antagonism_reduces_activity-based_anorexia_/10766627
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.
2016-02-17 00:00:00
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