title: Dopamine D2/3 receptor antagonism reduces activity-based anorexia.
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-HT(2A/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.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Klenotich
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Ho
authors.affiliation: Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: McMurray
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Server
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Dulawa
mesh_terms: D000077582:Amisulpride; D000818:Animals; D000856:Anorexia Nervosa / Q000188:drug therapy*; D001569:Benzodiazepines / Q000627:therapeutic use; D004195:Disease Models, Animal; D065127:Dopamine D2 Receptor Antagonists / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects; D005260:Female; D007211:Indoles / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects*; D009570:Nitriles / Q000627:therapeutic use; D000077152:Olanzapine; D010880:Piperidines / Q000627:therapeutic use; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000627:therapeutic use; D013469:Sulpiride / Q000031:analogs & derivatives / Q000627:therapeutic use; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D009570:Nitriles; D010880:Piperidines; D050637:Receptors, Dopamine D3; C409982:SB 277011; D012457:Salicylamides; D044005:Tetrahydroisoquinolines; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; C104750:3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole; C045989:eticlopride; D000077152:Olanzapine