title: A role for hypothalamic AMP-activated protein kinase in the mediation of hyperphagia and weight gain induced by chronic treatment with olanzapine in female rats.
abstract: Olanzapine is known to be advantageous with respect to outcome and drug compliance in patients with schizophrenia. However, olanzapine has adverse effects, including a higher incidence of weight gain and metabolic disturbances, when compared with those of other antipsychotic agents. The mechanisms underlying these adverse events remain obscure. Female rats were orally administered olanzapine (2 mg/kg) or vehicle once a day for 2 weeks to ascertain if hypothalamic AMP-activated protein kinase (AMPK) mediates olanzapine-induced weight gain and hyperphagia. Body weight and food intake in each rat were evaluated every day and every two days, respectively. After the termination of drug treatment, we measured the protein levels of AMPK and phosphorylated AMPK in the hypothalamus using western blot analyses. Olanzapine significantly increased body weight and food intake. The phosphorylation levels of AMPK were significantly elevated by olanzapine. These results suggest that activation of hypothalamic AMPK may mediate hyperphagia and weight gain induced by chronic treatment with olanzapine.
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Ei
authors.initials: E
authors.lastname: Sejima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishioku
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Koga
authors.forename: Kengo
authors.initials: K
authors.lastname: Nakagama
authors.forename: Shinya
authors.initials: S
authors.lastname: Dohgu
authors.forename: Kojiro
authors.initials: K
authors.lastname: Futagami
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006963:Hyperphagia / Q000139:chemically induced* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology*; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D055372:AMP-Activated Protein Kinases; D000077152:Olanzapine