title: Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine.
abstract: Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents.
authors.affiliation: The Norwegian Centre for Mental Disorders Research (NORMENT) and the K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway Dr Einar Martens' Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kari M
authors.initials: KM
authors.lastname: Ersland
authors.affiliation: The Norwegian Centre for Mental Disorders Research (NORMENT) and the K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway Dr Einar Martens' Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway silje.skrede@uib.no.
authors.forename: Silje
authors.initials: S
authors.lastname: Skrede
authors.affiliation: Department of Clinical Science, The Hormone Laboratory Research Group, University of Bergen, Bergen, Norway KG Jebsen Center for Diabetes Research, Haukeland University Hospital, Bergen, Norway.
authors.forename: Therese H
authors.initials: TH
authors.lastname: Røst
authors.affiliation: The Lipid Research Group, Section for Medical Biochemistry, Department of Clinical Science, University of Bergen, Bergen, Norway Department of Heart Disease, University of Bergen, Bergen, Norway.
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.affiliation: The Norwegian Centre for Mental Disorders Research (NORMENT) and the K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway Dr Einar Martens' Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Vidar M
authors.initials: VM
authors.lastname: Steen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006207:Half-Life; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018967:Risperidone; D000077152:Olanzapine
keywords: Antipsychotic; long-acting; metabolic; rat