title: Routine exercise ameliorates the metabolic side-effects of treatment with the atypical antipsychotic drug olanzapine in rats.
abstract: Second generation antipsychotic (SGA) drugs are effective treatments for psychosis. Common side-effects of SGAs include metabolic dysregulation and risk of cardiometabolic disorders. Metabolic side-effects, including glucose intolerance, can be accurately modelled in rodents. The benefits of interventions used for treating metabolic side-effects of SGAs are mostly unknown. In a 9 wk longitudinal study, female rats were given daily olanzapine (10 mg/kg s.c.) or vehicle. Animals were either sedentary or allowed 1 or 3 h daily access to a running wheel, with total wheel revolutions electronically quantified to reflect exercise intensity. Glucose tolerance tests were performed once weekly to measure glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured. Exercise intensity progressively increased over time in all groups given access to running wheels; however, rats treated with olanzapine consistently exercised less than those given the vehicle. Olanzapine caused acute and persistent glucose intolerance throughout the study, which was markedly, though incompletely, ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle-treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of GLUT4 in skeletal muscle were higher in both groups of exercising than in sedentary rats, and GLUT4 values were negatively correlated with glucose intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter that mediates glucose uptake into cells. The current animal model is suitable for evaluating physiological pathways involved with glucose intolerance.
authors: Department of Pharmacology, University of British Columbia, 2176 Health Sciences Mall, Vancouver, B.C., V6T 1Z3, Canada.
authors: H N
authors: HN
authors: Boyda
authors: A
authors: A
authors: Ramos-Miguel
authors: R M
authors: RM
authors: Procyshyn
authors: E
authors: E
authors: Töpfer
authors: N
authors: N
authors: Lant
authors: H H T
authors: HH
authors: Choy
authors: R
authors: R
authors: Wong
authors: L
authors: L
authors: Li
authors: C C Y
authors: CC
authors: Pang
authors: W G
authors: WG
authors: Honer
authors: A M
authors: AM
authors: Barr
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000097:blood; D001569:Benzodiazepines / Q000009:adverse effects* / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D000077152:Olanzapine; D051381:Rats
chemical_list: D014150:Antipsychotic Agents; D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; D001569:Benzodiazepines; D000077152:Olanzapine