Background: A major untoward side effect of antipsychotic treatment is weight gain. Patients that gain excessive weight are at increased risk of developing morbidities and they may discontinue their treatment regimen. There are no established rodent models for this effect. Hypothesis: Olanzapine will induce weight gain in mice due to increased food intake and decreased energy expenditure resulting in increased body fat.
Specific Aims : (1) Measure energy intake during short term and long term treatments. (2) Measure RMR, RQ, activity, and body composition. (3) Evaluate fasting and MTII effects on the weight gain model. (4) Measure serum biomarkers. (5) Measure gene expression in hypothalamus using quantitative RT-PCR. Methods: Evaluate effects of olanzapine on weight gain, appetite, RMR, RQ, and body composition by measuring body weights, assessing food intake, performing indirect calorimetry, and using DXA, respectively. Design: Female C57BL/6J mice will be administered olanzapine or placebo via peanut butter for four weeks with blood and hypothalami samples taken at the end. DXA, RQ, and RMR will be measured prior to and after drug administration. Body weights and food intake will be measured cumulatively during experiments. Summary: Analysis of food intake, serum markers, hypothalami gene expression, RMR, RQ, activity and body composition from these experiments will aid in understanding the energetics of atypical antipsychotic-induced weight gain.
| Li, Xingsheng; Cope, Mark B; Johnson, Maria S et al. (2010) Mild calorie restriction induces fat accumulation in female C57BL/6J mice. Obesity (Silver Spring) 18:456-62 |
| Cope, Mark B; Li, Xingsheng; Jumbo-Lucioni, Patricia et al. (2009) Risperidone alters food intake, core body temperature, and locomotor activity in mice. Physiol Behav 96:457-63 |
| Cope, M B; Jumbo-Lucioni, P; Walton, R G et al. (2007) No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs. Int J Obes (Lond) 31:1014-22 |
