title: Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats.
abstract: The atypical antipsychotic drug olanzapine increases body weight and visceral adiposity in schizophrenia. In rats, aging-associated increased body weight and visceral adiposity are reversed by administration of the pineal hormone melatonin. We asked if melatonin similarly would reverse olanzapine-induced increased weight and visceral adiposity in rats. Four groups (n=11/group) of female rats (240-250 g) were treated for 8 weeks with olanzapine, melatonin, olanzapine+melatonin, or vehicle alone in drinking water. Body weight and food and water consumption were determined weekly, locomotor activity at weeks 3 and 6, and nocturnal plasma melatonin concentration at week 7. At week 8, the rats were killed and visceral (perirenal, retroperitoneal, omental, and mesenteric) fat pads dissected and weighed. Olanzapine treatment reduced nocturnal plasma melatonin by 55% (p<0.001), which was restored to control levels by olanzapine+melatonin. Body weight increased 18% in rats treated with olanzapine alone, but only 10% with olanzapine+melatonin, 5% with melatonin alone, and 7% with vehicle control. Body weight and visceral fat pad weight increases in rats treated with olanzapine alone were greater than in each of the other three groups (all p<0.01), which were not significantly different. These results suggest that olanzapine-induced increases in body weight and visceral adiposity may be at least in part secondary to olanzapine-induced reduction of plasma melatonin levels, and that melatonin may be useful for the management of olanzapine-induced weight gain in humans.
authors.affiliation: VA Puget Sound Health Care System, Mental Illness Research, Education and Clinical Center, Seattle, WA 98108, USA.
authors.forename: Murray A
authors.initials: MA
authors.lastname: Raskind
authors.forename: Brianna L
authors.initials: BL
authors.lastname: Burke
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Crites
authors.forename: Andre M
authors.initials: AM
authors.lastname: Tapp
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Rasmussen
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008550:Melatonin / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000077152:Olanzapine; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000188:drug therapy; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D008550:Melatonin; D000077152:Olanzapine