title: Chronic treatment with olanzapine via a novel infusion pump induces adiposity in male rats.
abstract: OBJECTIVE
  Clinical use of olanzapine has been suggested to be associated with weight gain and adiposity in schizophrenic patients. While studies in experimental animals have noted weight gain in olanzapine-treated female rats, these findings have yet to be replicated in males. This study investigated the effect of chronic subcutaneous infusion of olanzapine in male rats via a recently developed electrical microinfusion pump.
  
  
  METHODS
  An electrical microinfusion pump was subcutaneously implanted in male Sprague-Dawley rats who were then chronically administered olanzapine. Plasma olanzapine concentration and body weight were monitored, and fat pads were weighed after six weeks' olanzapine treatment.
  
  
  RESULTS
  Plasma olanzapine concentration plateaued within 4h of commencement of chronic olanzapine 1.5mg/animal/day infusion and remained constant until day 21. Six-week infusion of olanzapine at 1.5 but not 1mg/animal/day induced significant adiposity in subcutaneous, epididymal, and retroperitoneal fat. Body weight and food intake values did not differ between olanzapine- and vehicle-treated rats throughout the experiment.
  
  
  CONCLUSIONS
  The present study demonstrated that chronic infusion of olanzapine induced adiposity in male rats without inducing weight gain or hyperphagia, even with sufficient plasma concentration. This report is the first to provide information about adiposity-inducible plasma concentration of olanzapine in male rats.
authors.affiliation: Pharmacology Research Labs, Astellas Pharma Inc., Miyukigaoka 21, Tsukuba, Ibaraki, Japan. miwako.shobo@jp.astellas.com
authors.forename: Miwako
authors.initials: M
authors.lastname: Shobo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Akiko
authors.initials: A
authors.lastname: Koakutsu
authors.forename: Noritaka
authors.initials: N
authors.lastname: Hamada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
authors.forename: Katsuya
authors.initials: K
authors.lastname: Harada
authors.forename: Keni
authors.initials: K
authors.lastname: Ni
authors.forename: Nobuya
authors.initials: N
authors.lastname: Matsuoka
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine