Olanzapine reduces physical activity in rats exposed to activity-based anorexia: possible implications for treatment of anorexia nervosa?
BACKGROUND
Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduces the development of ABA in rats. The effect of olanzapine treatment in AN patients was also evaluated in a small open-label study.


METHODS
Rats were chronically (1 week) infused with olanzapine (7.5 mg/kg) and exposed to the ABA model or ad libitum feeding. Hyperactive AN patients were followed for up to 3 months of olanzapine treatment (5 mg/kg).


RESULTS
Olanzapine treatment reduced development of ABA in rats by reducing running wheel activity, starvation-induced hypothermia and activation of the hypothalamus-pituitary-adrenal axis. Olanzapine treatment reduced activity levels of AN patients compared with untreated AN patients, without affecting body weight and plasma leptin levels.


CONCLUSIONS
Olanzapine treatment reduced wheel running and thereby diminished development of ABA in rats. Olanzapine treatment also reduced physical activity in hyperactive AN patients in a small open-label study. These data support the need for controlled studies investigating the putative beneficial effects of olanzapine treatment in AN patients.
Hillebrand
Jacquelien J G
JJ
Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
van Elburg
Annemarie A
AA
Kas
Martien J H
MJ
van Engeland
Herman
H
Adan
Roger A H
RA
D000273:Adipose Tissue / Q000187:drug effects; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000855:Anorexia / Q000188:drug therapy* / Q000503:physiopathology; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001522:Behavior, Animal; D001569:Benzodiazepines / Q000008:administration & dosage; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D000077152:Olanzapine; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012420:Running; D013997:Time Factors
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000324:Adrenocorticotropic Hormone; D000077152:Olanzapine; D003345:Corticosterone