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Olanzapine treatment and metabolic dysfunction: a dose response study in female Sprague Dawley rats
- Source :
-
Behavioural Brain Research . Mar2011, Vol. 217 Issue 2, p337-346. 10p. - Publication Year :
- 2011
-
Abstract
- Abstract: Second generation antipsychotics are commonly prescribed for the treatment of schizophrenia, however some can induce metabolic dysfunction side-effects such as weight gain, obesity and diabetes. Clinical reports suggest olanzapine alters satiety signals, although findings appear conflicting. Previous animal model studies have utilised a range of olanzapine dosages, however the dosage that better mimics the human scenario of olanzapine-induced weight gain is unclear. Female Sprague–Dawley rats were treated orally, three times daily with olanzapine (0.25mg/kg, 0.5mg/kg, 1.0mg/kg, 2.0mg/kg), self-administered in a sweet cookie dough pellet at eight-hourly intervals) or vehicle (n =12/group) for 14-days. Olanzapine orally self-administered in multiple doses (eight-hourly intervals) may circumvent a drop in plasma drug concentration and ensure the maintenance of a consistently high olanzapine level in the rat. Olanzapine increased body weight (0.5mg/kg, 1.0mg/kg, 2.0mg/kg), food intake (2.0mg/kg) and feeding efficiency (0.5–2.0mg/kg), with no effect on water intake. Subcutaneous inguinal (1.0mg/kg, 2.0mg/kg) and intra-abdominal perirenal fat were increased (2.0mg/kg), but not interscapula brown adipose tissue. Olanzapine increased circulating ghrelin and cholecystokinin, but had no effect on peptide YY(3–36). Olanzapine decreased insulin (0.25–2.0mg/kg) and locomotor activity in the open field arena (0.5–2.0mg/kg). A low dosage of 0.25mg/kg olanzapine had no effect on most parameters measured. Olanzapine-induced weight gain is associated with hyperphagia, enhanced feeding efficiency and adiposity, decreased locomotor activity and altered satiety signaling. The animal model used in the present study of self-administered oral olanzapine treatment (t.i.d.) at a dosage range of 0.5–2.0mg/kg (but not 0.25mg/kg) mimics aspects of the clinic. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01664328
- Volume :
- 217
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Behavioural Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 57076114
- Full Text :
- https://doi.org/10.1016/j.bbr.2010.10.039